Mutant BIN1-Dynamin 2 complexes dysregulate membrane remodeling in the pathogenesis of centronuclear myopathy
2021; Elsevier BV; Volume: 296; Linguagem: Inglês
10.1074/jbc.ra120.015184
ISSN1083-351X
AutoresKenshiro Fujise, Mariko Okubo, Tadashi Abe, Hiroshi Yamada, Ichizo Nishino, S. Noguchi, Kohji Takei, Tetsuya Takeda,
Tópico(s)Genetic Neurodegenerative Diseases
ResumoMembrane remodeling is required for dynamic cellular processes such as cell division, polarization, and motility. BAR domain proteins and dynamins are key molecules in membrane remodeling that work together for membrane deformation and fission. In striated muscles, sarcolemmal invaginations termed T-tubules are required for excitation–contraction coupling. BIN1 and DNM2, which encode a BAR domain protein BIN1 and dynamin 2, respectively, have been reported to be causative genes of centronuclear myopathy (CNM), a hereditary degenerative disease of skeletal muscle, and deformation of T-tubules is often observed in the CNM patients. However, it remains unclear how BIN1 and dynamin 2 are implicated in T-tubule biogenesis and how mutations in these molecules cause CNM to develop. Here, using an in cellulo reconstitution assay, we demonstrate that dynamin 2 is required for stabilization of membranous structures equivalent to T-tubules. GTPase activity of wild-type dynamin 2 is suppressed through interaction with BIN1, whereas that of the disease-associated mutant dynamin 2 remains active due to lack of the BIN1-mediated regulation, thus causing aberrant membrane remodeling. Finally, we show that in cellulo aberrant membrane remodeling by mutant dynamin 2 variants is correlated with their enhanced membrane fission activities, and the results can explain severity of the symptoms in patients. Thus, this study provides molecular insights into dysregulated membrane remodeling triggering the pathogenesis of DNM2-related CNM. Membrane remodeling is required for dynamic cellular processes such as cell division, polarization, and motility. BAR domain proteins and dynamins are key molecules in membrane remodeling that work together for membrane deformation and fission. In striated muscles, sarcolemmal invaginations termed T-tubules are required for excitation–contraction coupling. BIN1 and DNM2, which encode a BAR domain protein BIN1 and dynamin 2, respectively, have been reported to be causative genes of centronuclear myopathy (CNM), a hereditary degenerative disease of skeletal muscle, and deformation of T-tubules is often observed in the CNM patients. However, it remains unclear how BIN1 and dynamin 2 are implicated in T-tubule biogenesis and how mutations in these molecules cause CNM to develop. Here, using an in cellulo reconstitution assay, we demonstrate that dynamin 2 is required for stabilization of membranous structures equivalent to T-tubules. GTPase activity of wild-type dynamin 2 is suppressed through interaction with BIN1, whereas that of the disease-associated mutant dynamin 2 remains active due to lack of the BIN1-mediated regulation, thus causing aberrant membrane remodeling. Finally, we show that in cellulo aberrant membrane remodeling by mutant dynamin 2 variants is correlated with their enhanced membrane fission activities, and the results can explain severity of the symptoms in patients. Thus, this study provides molecular insights into dysregulated membrane remodeling triggering the pathogenesis of DNM2-related CNM. Centronuclear myopathy (CNM) is a congenital myopathy characterized clinically by muscle weakness and pathologically by the presence of centralized nuclei on muscle biopsy (1Jungbluth H. Wallgren-Pettersson C. Laporte J. Centronuclear (myotubular) myopathy.Orphanet J. Rare Dis. 2008; 3: 26Crossref PubMed Scopus (217) Google Scholar). Disrupted or disorganized T-tubules or triads in the skeletal muscles are also common pathological observations in CNM tissue (2Al-Qusairi L. Laporte J. T-tubule biogenesis and triad formation in skeletal muscle and implication in human diseases.Skelet. Muscle. 2011; 1: 26Crossref PubMed Scopus (109) Google Scholar). BIN1, which encodes an N-terminal amphipathic helix Bin/Amphiphysin/Rvs-homology (N-BAR) domain protein BIN1 (Bridging integrator 1)/Amphiphysin 2, has been identified as one of the causative genes for this disease (3Nicot A.S. Toussaint A. Tosch V. Kretz C. Wallgren-Pettersson C. Iwarsson E. Kingston H. Garnier J.M. Biancalana V. Oldfors A. Mandel J.L. Laporte J. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy.Nat. Genet. 2007; 39: 1134-1139Crossref PubMed Scopus (280) Google Scholar, 4Bohm J. Yis U. Ortac R. Cakmakci H. Kurul S.H. Dirik E. Laporte J. Case report of intrafamilial variability in autosomal recessive centronuclear myopathy associated to a novel BIN1 stop mutation.Orphanet J. Rare Dis. 2010; 5: 35Crossref PubMed Scopus (40) Google Scholar, 5Claeys K.G. Maisonobe T. Bohm J. Laporte J. Hezode M. Romero N.B. Brochier G. Bitoun M. 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Sabe H. Regulation of Bin1 SH3 domain binding by phosphoinositides.EMBO J. 2004; 23: 4413-4422Crossref PubMed Scopus (60) Google Scholar). To date, two recessive CNM mutations, p.Q573∗ and p.K575∗ (p.Q434∗ and p.K436∗ in isoform 8), have been identified in CNM patients, and both mutations cause truncation of the SH3 domain. In fact, the p.K436∗ mutation was shown to abolish the BIN1–dynamin 2 interaction and recruitment of dynamin 2 to the BIN1-mediated T-tubule-like structures (TLS) (3Nicot A.S. Toussaint A. Tosch V. Kretz C. Wallgren-Pettersson C. Iwarsson E. Kingston H. Garnier J.M. Biancalana V. Oldfors A. Mandel J.L. Laporte J. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy.Nat. 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Increased expression of wild-type or a centronuclear myopathy mutant of dynamin 2 in skeletal muscle of adult mice leads to structural defects and muscle weakness.Am. J. Pathol. 2011; 178: 2224-2235Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar, 24Durieux A.C. Vignaud A. Prudhon B. Viou M.T. Beuvin M. Vassilopoulos S. Fraysse B. Ferry A. Laine J. Romero N.B. Guicheney P. Bitoun M. A centronuclear myopathy-dynamin 2 mutation impairs skeletal muscle structure and function in mice.Hum. Mol. Genet. 2010; 19: 4820-4836Crossref PubMed Scopus (92) Google Scholar, 25Cowling B.S. Chevremont T. Prokic I. Kretz C. Ferry A. Coirault C. Koutsopoulos O. Laugel V. Romero N.B. Laporte J. Reducing dynamin 2 expression rescues X-linked centronuclear myopathy.J. Clin. Invest. 2014; 124: 1350-1363Crossref PubMed Scopus (93) Google Scholar) and is thought to be involved in determination of the T-tubule orientation (26Cowling B.S. Prokic I. Tasfaout H. Rabai A. Humbert F. Rinaldi B. 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Lee A. Kan H.W. Laiman J. Chuang M.C. Hsieh S.T. Liu Y.W. Dynamin-2 mutations associated with centronuclear myopathy are hypermorphic and lead to T-tubule fragmentation.Hum. Mol. Genet. 2015; 24: 5542-5554Crossref PubMed Scopus (39) Google Scholar). These data suggest that CNM-associated mutations in BIN1 and DNM2 might affect membrane remodeling activities of their protein products leading to aberrant formation and/or maintenance of the T-tubules in CNM muscles. However, the exact molecular mechanism of this defective membrane remodeling arising from these genetic mutations remains to be clearly elucidated. In this study, using an in cellulo reconstitution assay, we show that wild-type dynamin 2 interacts with BIN1 to stabilize the BIN1-mediated TLS in mouse myoblast C2C12 cells. GTPase activity of dynamin 2 is suppressed by interaction with BIN1 enabling its stabilizing function of the TLS. In contrast, CNM-associated mutations in dynamin 2 produce constitutive active GTPase activity due to enhanced self-assembly and impaired GTPase suppression by BIN1. Interestingly, these results are consistent with a gain of function (GOF) of mutant dynamin 2 to establish the correlation between cellulotypes and disease phenotypes. Our results suggest that aberrant regulation of membrane remodeling by BIN1-dynamin 2 complex is tightly linked to the pathogenesis of CNM. See Figures 1 through 5. BIN1 interacts with dynamin 2 and their cooperative function is implicated in T-tubule formation (3Nicot A.S. Toussaint A. Tosch V. Kretz C. Wallgren-Pettersson C. Iwarsson E. Kingston H. Garnier J.M. Biancalana V. Oldfors A. Mandel J.L. Laporte J. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy.Nat. Genet. 2007; 39: 1134-1139Crossref PubMed Scopus (280) Google Scholar, 14Lee E. Marcucci M. Daniell L. Pypaert M. Weisz O.A. Ochoa G.C. Farsad K. Wenk M.R. De Camilli P. Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle.Science. 2002; 297: 1193-1196Crossref PubMed Scopus (323) Google Scholar), yet the precise role of dynamin 2 was unclear. To examine dynamin 2 function in T-tubule formation, we analyzed the effect of dynamin 2 overexpression using in cellulo reconstitution assay for TLS (3Nicot A.S. Toussaint A. Tosch V. Kretz C. Wallgren-Pettersson C. Iwarsson E. Kingston H. Garnier J.M. Biancalana V. Oldfors A. Mandel J.L. Laporte J. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy.Nat. Genet. 2007; 39: 1134-1139Crossref PubMed Scopus (280) Google Scholar, 7Bohm J. Biancalana V. Malfatti E. Dondaine N. Koch C. Vasli N. Kress W. Strittmatter M. Taratuto A.L. Gonorazky H. Laforet P. Maisonobe T. Olive M. Gonzalez-Mera L. Fardeau M. et al.Adult-onset autosomal dominant centronuclear myopathy due to BIN1 mutations.Brain. 2014; 137: 3160-3170Crossref PubMed Scopus (62) Google Scholar, 14Lee E. Marcucci M. Daniell L. Pypaert M. Weisz O.A. Ochoa G.C. Farsad K. Wenk M.R. De Camilli P. Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle.Science. 2002; 297: 1193-1196Crossref PubMed Scopus (323) Google Scholar, 29Picas L. Viaud J. Schauer K. Vanni S. Hnia K. Fraisier V. Roux A. Bassereau P. Gaits-Iacovoni F. Payrastre B. Laporte J. Manneville J.B. Goud B. BIN1/M-amphiphysin2 induces clustering of phosphoinositides to recruit its downstream partner dynamin.Nat. Commun. 2014; 5: 5647Crossref PubMed Scopus (71) Google Scholar). Consistent with previous studies (3Nicot A.S. Toussaint A. Tosch V. Kretz C. Wallgren-Pettersson C. Iwarsson E. Kingston H. Garnier J.M. Biancalana V. Oldfors A. Mandel J.L. Laporte J. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy.Nat. Genet. 2007; 39: 1134-1139Crossref PubMed Scopus (280) Google Scholar, 7Bohm J. Biancalana V. Malfatti E. Dondaine N. Koch C. Vasli N. Kress W. Strittmatter M. Taratuto A.L. Gonorazky H. Laforet P. Maisonobe T. Olive M. Gonzalez-Mera L. Fardeau M. et al.Adult-onset autosomal dominant centronuclear myopathy due to BIN1 mutations.Brain. 2014; 137: 3160-3170Crossref PubMed Scopus (62) Google Scholar, 14Lee E. Marcucci M. Daniell L. Pypaert M. Weisz O.A. Ochoa G.C. Farsad K. Wenk M.R. De Camilli P. Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle.Science. 2002; 297: 1193-1196Crossref PubMed Scopus (323) Google Scholar, 29Picas L. Viaud J. Schauer K. Vanni S. Hnia K. Fraisier V. Roux A. Bassereau P. Gaits-Iacovoni F. Payrastre B. Laporte J. Manneville J.B. Goud B. BIN1/M-amphiphysin2 induces clustering of phosphoinositides to recruit its downstream partner dynamin.Nat. Commun. 2014; 5: 5647Crossref PubMed Scopus (71) Google Scholar), BIN1 overexpression in C2C12 cells induced numerous TLS, on which BIN1 was highly concentrated (Fig. 1A), whereas overexpressed dynamin 2 was found to be evenly distributed in cytoplasm of C2C12 cells (Fig. 4B, DNM2WT-FLAG). In contrast, when BIN1 and dynamin 2 were coexpressed, dynamin 2 was recruited to the BIN1-mediated TLS, and thick and unevenly distributed membrane tubules were induced (Fig. 1B). Consistent with previous studies (14Lee E. Marcucci M. Daniell L. Pypaert M. Weisz O.A. Ochoa G.C. Farsad K. Wenk M.R. De Camilli P. Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle.Science. 2002; 297: 1193-1196Crossref PubMed Scopus (323) Google Scholar, 29Picas L. Viaud J. Schauer K. Vanni S. Hnia K. Fraisier V. Roux A. Bassereau P. Gaits-Iacovoni F. Payrastre B. Laporte J. Manneville J.B. Goud B. BIN1/M-amphiphysin2 induces clustering of phosphoinositides to recruit its downstream partner dynamin.Nat. Commun. 2014; 5: 5647Crossref PubMed Scopus (71) Google Scholar), these TLS appeared to be membranous structures that could be counter stained with a fluorescent membrane dye DiO (Fig. S1A). We also examined the membrane tubules reconstituted in vitro by electron microscopy. Purified BIN1 alone (Fig. S1B, BIN1 WT) or in combination with purified dynamin 2 (Fig. S1B, Dynamin 2 WT) resulted in formation of similar membrane-associated tubular structures (Fig. S1C). We next examined whether BIN1 and BIN1+Dynamin tubules have similar dynamic properties. We observed TLS formed by sole BIN1 overexpression to be highly dynamic (Fig. 1C; Movie S1), whereas those with dynamin 2 were static (Fig. 1D; Movie S2). Kymograph analyses showed that the TLS formed by BIN1 alone repeatedly grew and shrank with average speed of 0.04 μm/s (n = 36) and 0.07 μm/s (n = 38), respectively (Fig. 1, E–F, BIN1-GFP). In contrast, the TLS almost stalled (growth: 0.01 μm/s (n = 9) and shrink: 0.01 μm/s (n = 8)) when dynamin 2 is coexpressed (Fig. 1, E–F, BIN1-GFP + DNM2-RFP). These results suggest that dynamin 2 might play a novel role in stabilizing TLS arising from BIN1 overexpression. To determine if dynamin 2 is indeed a stabilizer of the TLS, endogenous dynamin 2 in C2C12 cells was depleted by RNAi and its effect on TLS formation was analyzed. In control RNAi cells, numerous long BIN1-mediated TLS were formed and endogenous dynamin 2 was recruited to them (Fig. 2A, siCtrl) in the same manner as exogenously expressed human dynamin 2 (Fig. 1B). In contrast, formation of the TLS was strongly inhibited in dynamin 2 RNAi cells (Fig. 2A, siDnm2). Quantitative analyses showed that the relative amount of long TLS (≥5 μm) in dynamin 2 RNAi cells was significantly decreased (3.4 ± 0.4%) compared with that in control RNAi cells (10.3 ± 2.4%) (Fig. 2B). The efficiency of dynamin 2 depletion by RNAi was confirmed by immunoblot analysis (Fig. 2C). These results show that dynamin 2 is required for formation of stable TLS induced by BIN1 overexpression. Previous studies demonstrated that PRD of dynamin 2 directly binds to SH3 domain of BIN1 (3Nicot A.S. Toussaint A. Tosch V. Kretz C. Wallgren-Pettersson C. Iwarsson E. Kingston H. Garnier J.M. Biancalana V. Oldfors A. Mandel J.L. Laporte J. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy.Nat. Genet. 2007; 39: 1134-1139Crossref PubMed Scopus (280) Google Scholar). However, the contribution of their interaction in T-tubule biogenesis was unclear. To determine if the interaction between dynamin 2 and BIN1 is required for TLS formation, full length or a PRD truncated form of human dynamin 2 was exogenously expressed and their abilities to rescue dynamin 2 RNAi phenotypes were measured. Exogenously expressed FLAG-tagged human dynamin 2 completely rescued dynamin 2 RNAi phenotype in C2C12 cells with numerous TLS reconstituted to the same level as in control RNAi cells (11.5 ± 0.9%) (Fig. 2, A–B, siDnm2+DNM2-FLAG). In contrast, the PRD-truncated form of human dynamin 2 failed to rescue the membrane tubulation defects in dynamin 2 RNAi cells (3.4 ± 0.6%) (Fig. 2, A–B, siDnm2+DNM2ΔPRD-FLAG). Expression levels of exogenously expressed FLAG-tagged human dynamin 2 (wild-type and ΔPRD) in these experiments were confirmed by immunoblotting (Fig. 2C). Finally, we reconfirmed that full-length dynamin 2, but not PRD-truncated, human dynamin 2 binds to BIN1 by coimmunoprecipitation assay (Fig. 2D). These results suggest that interaction between dynamin 2 and BIN1 is required for formation of stable TLS. The protein encoded by an autosomal recessive CNM mutant of BIN1 harboring a nonsense mutations in the SH3 domain, p.K575∗ (p.K436∗ in isoform 8), had previously been shown to have reduced binding affinity with dynamin 2 (3Nicot A.S. Toussaint A. Tosch V. Kretz C. Wallgren-Pettersson C. Iwarsson E. Kingston H. Garnier J.M. Biancalana V. Oldfors A. Mandel J.L. Laporte J. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy.Nat. Genet. 2007; 39: 1134-1139Crossref PubMed Scopus (280) Google Scholar). To examine if this alteration in the interaction between BIN1 and dynamin 2 is responsible for CNM pathogenesis, we examined TLS arising from the overexpression of CNM mutant BIN1 in SH3 domain (Fig. 3A). As described above, wild-type BIN1 induced numerous long TLS in C2C12 cells (Fig. 3B, BIN1WT-GFP). In contrast, BIN1 harboring the CNM mutations in SH3 domain, K436X and Q434X (dubbed BIN1Δ436–454 and BIN1Δ434–454, respectively), formed short and abnormally aggregated TLS (Fig. 3B, BIN1Δ436–454-GFP and BIN1Δ434–454-GFP). Quantitative analyses showed that the proportion of long TLS (≥5 μm) formed by wild-type BIN1 (10.2 ± 0.7%) was reduced when BIN1Δ436–454 or BIN1Δ434–454 was used (6.1% ± 1.8% and 6.3 ± 0.7%, respectively) (Fig. 3C). Consistent with the previous observations (3Nicot A.S. Toussaint A. Tosch V. Kretz C. Wallgren-Pettersson C. Iwarsson E. Kingston H. Garnier J.M. Biancalana V. Oldfors A. Mandel J.L. Laporte J. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy.Nat. Genet. 2007; 39: 1134-1139Crossref PubMed Scopus (280) Google Scholar), CNM mutant BIN1 (BIN1Δ436–454 and BIN1Δ434–454), as well as BIN1 H435X (BIN1Δ435–454) where histidine at codon 435 was substituted with a premature termination codon, exhibited reduced binding affinity with dynamin 2 (Fig. 3D). Defective interaction of the CNM mutant BIN1 (BIN1Δ436–454 and BIN1Δ434–454) with dynamin 2 was also confirmed by reciprocal immunoprecipitation of GFP-tagged BIN1 using GFP-Trap (Fig. S2). These data suggest that physical interaction of dynamin 2 with BIN1 is required for formation of the TLS and their defective interaction is associated with CNM pathogenesis. We next examined localization and function of four previously reported dynamin 2 CNM mutants (Fig. 4A) using the in cellulo TLS reconstitution assay. DNM2-related CNM patients typically present milder and slowly progressive symptoms and favorable prognosis, with an age of onset that varies from infantile to adolescence. Among the CNM mutations examined, E368K and S619W are known to be associated with more severe phenotypes (neonatal to childhood onset), whereas R369W and R465W are associated with milder symptoms and later onset (adolescence to adulthood) (30Bohm J. Biancalana V. Dechene E.T. Bitoun M. Pierson C.R. Schaefer E. Karasoy H. Dempsey M.A. Klein F. Dondaine N. Kretz C. Haumesser N. Poirson C. Toussaint A. Greenleaf R.S. et al.Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy.Hum. Mutat. 2012; 33: 949-959Crossref PubMed Scopus (94) Google Scholar, 31Hohendahl A. Roux A. Galli V. Structural insights into the centronuclear myopathy-associated functions of BIN1 and dynamin 2.J. Struct. Biol. 2016; 196: 37-47Crossref PubMed Scopus (19) Google Scholar). In C2C12 cells, FLAG-tagged wild-type dynamin 2 formed very fine puncta with some accumulation at the leading edge (Fig. 4B, DNM2WT-FLAG). In contrast, cells expressing mutant dynamin 2, with missense mutations either in the stalk (E368K, R369W and R465W) or in the PH domain (S619W), formed abnormally larger puncta with strong accumulation at the leading edges (Fig. 4B, DNM2E368K-FLAG, DNM2R369W-FLAG, DNM2R465W-FLAG, and DNM2S619W-FLAG). The effects of these mutant dynamin 2 forms on TLS formation were also examined. As described above, we observed wild-type dynamin 2 induced and was recruited to unevenly distributed membranous TLS (Fig. 4C, DNM2WT-FLAG). In contrast, mutant dynamin 2 induced shorter and more evenly distributed TLS despite still being colocalized with BIN1 (Fig. 4C, DNM2E368K-FLAG, DNM2R369W-FLAG, DNM2R465W-FLAG, and DNM2S619W-FLAG). Quantitative analyses showed that the proportion of the long TLS (≥5 μm) formed in the presence of mutant dynamin 2 was reduced (E368K: 4.5 ± 1.3%; R369W: 5.7 ± 1.7%; R465W: 7.6 ± 2.0%; S619W: 4.6 ± 1.0%) compared with that of wild-type dynamin 2 (10.6 ± 0.9%) (Fig. 4D). This is consistent with a possible overfission of the TLS. Indeed, overexpression of mutant dynamin 2 induced slightly decreased number of long TLS (≥5 μm) (Fig. 4E) and significantly increased number of short TLS (1 μm ≤ and < 5 μm) (Fig. 4F), although the statistical significance of this was modest. Taken together, these results suggest that mutant dynamin 2 variants exhibit enhanced membrane fission activities and different levels of aberrant dynamics that correlate with the severity of the symptoms in patients. To further investigate the mechanisms of TLS formation by mutant dynamin 2, we examined a stalk domain mutant (E368K) and a PH domain mutant (S619W) for their self-assembly and GTPase activity, both of which are essential for membrane fission by dynamin (32Warnock D.E. Hinshaw J.E. Schmid S.L. Dynamin self-assembly stimulates its GTPase activity.J. Biol. Chem. 1996; 271: 22310-22314Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar, 33Marks B. Stowell M.H. Vallis Y. Mills I.G. Gibson A. Hopkins C.R. McMahon H.T. GTPase activity of dynamin and resulting conformation change are essential for endocytosis.Nature. 2001; 410: 231-235Crossref PubMed Scopus (375) Google Scholar). Previous studies demonstrated that dynamin is self-assembled in a low salt condition and is disassembled in the presence of GTP (34Ramachandran R. Surka M. Chappie J.S. Fowler D.M. Foss T.R. Song B.D. Schmid S.L. The dynamin middle domain is critical for tetramerization and higher-order self-assembly.EMBO J. 2007; 26: 559-566Crossref PubMed Scopus (137) Google Scholar, 35Wang L. Barylko B. Byers C. Ross J.A. Jameson D.M. Albanesi J.P. Dynamin 2 mutants linked to centronuclear myopathies form abnormally stable polymers.J. Biol. Chem. 2010; 285: 22753-22757Abstract Full Text Full Text PDF PubMed Scopus (56) Goo
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