The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor binds and mediates catabolism of bovine milk lipoprotein lipase.
1992; Elsevier BV; Volume: 267; Issue: 36 Linguagem: Inglês
10.1016/s0021-9258(18)35675-8
ISSN1083-351X
AutoresDavid Chappell, Glenna L. Fry, Michelle Waknitz, Per‐Henrik Iverius, Suzanne E. Williams, Dudley K. Strickland,
Tópico(s)Muscle metabolism and nutrition
ResumoLipoprotein lipase (LPL), the major lipolytic enzyme involved in the conversion of triglyceride-rich lipoproteins to remnants, was found to compete with binding of activated a2-macroglobulin (a2M*) to the low density lipoprotein receptor-related protein (LRP)/a2-macroglobulin receptor.Bovine milk LPL displaced both 1251-labeled a2M* and 39-kDa azM receptor-associated protein (RAP) from the surface of cultured mutant fibroblasts lacking LDL receptors with apparent K , values at 4 "C of 6.8 and 30 nM, respectively.Furthermore, LPL inhibited the cellular degradation of 1251-a2M* at 37 "C.Because both a2M* and RAP interact with LRP, these data suggest that LPL binds specifically to this receptor.This was further supported by observing that an immunoaffinity-isolated polyclonal antibody against LRP blocked cellular degradation of '*'I-LPL in a dose-dependent manner.In addition, 1251-LPL bound to highly purified LRP in a solid-phase assay with a KO of 18 nM, and this binding could be partially displaced with a2M' ( K , = 7 nM) and RAP ( K , = 3 nM).Taken together, these data establish that LPL binds with high affinity to LRP and undergoes LRPmediated cellular uptake.The implication of these findings for lipoprotein catabolism in vivo may be important if LRP binding is preserved when LPL is attached to lipoproteins.If so, LPL might facilitate LRPmediated clearance of lipoproteins.Lipoprotein lipase (LPL)' is the major lipolytic enzyme involved in conversion of triglyceride-rich plasma lipoproteins to smaller remnants (1).Lipoprotein remnant clearance is a rapid process in vivo (t1r2 -20 min) and is mediated predominantly by hepatocytes (2, 3).For several years, it has been
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