The Src homology 3 domain of the beta-subunit of voltage-gated calcium channels promotes endocytosis via dynamin interaction
High voltage-gated calcium channels enable calcium entry into cells in response to membrane depolarization. Association of the auxiliary Î²-subunit to the Î±-interaction-domain in the pore-forming Î²1-subunit is required to form functional channels. The Î²-subunit belongs to the membrane-associated guanylate kinase class of scaffolding proteins containing a Src homology 3 and a guanylate kinase domain. Although the latter is responsible for the high affinity binding to the Î±-interaction domain, the functional significance of the Src homology 3 domain remains elusive. Here, we show that injection of isolated Î²-subunit Src homology 3 domain into Xenopus laevis oocytes expressing the Î±1-subunit reduces the number of channels in the plasma membrane. This effect is reverted by coexpressing Î±1 with a dominant-negative mutant of dynamin, a GTPase involved in receptor-mediated endocytosis. Full-length Î²-subunit also down-regulates voltage-gated calcium channels but only when lacking the Î±-interaction domain. Moreover, isolated Src homology 3 domain and the full-length Î²-subunit were found to interact in vitro with dynamin and to internalize the distantly related Shaker potassium channel. These results demonstrate that the Î²-subunit regulates the turnover of voltage-gated calcium channels and other proteins in the cell membrane. This effect is mediated by dynamin and depends on the association state of the Î²-subunit to the Î±1-pore-forming subunit. Our findings define a novel function for the Î²-subunit through its Src homology 3 domain and establish a link between voltage-gated calcium channel activity and the cell endocytic machinery. Â© 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
|Título según WOS:||The Src homology 3 domain of the beta-subunit of voltage-gated calcium channels promotes endocytosis via dynamin interaction|
|Título según SCOPUS:||The Src homology 3 domain of the ß-subunit of voltage-gated calcium channels promotes endocytosis via dynamin interaction|
|Título de la Revista:||JOURNAL OF BIOLOGICAL CHEMISTRY|
|Fecha de publicación:||2007|
|Página de inicio:||2156|