The Src homology 3 domain of the beta-subunit of voltage-gated calcium channels promotes endocytosis via dynamin interaction

Gonzalez-Gutierrez G.; Miranda-Laferte E.; Neely A.; Hidalgo, P.

Abstract

High voltage-gated calcium channels enable calcium entry into cells in response to membrane depolarization. Association of the auxiliary β-subunit to the α-interaction-domain in the pore-forming β1-subunit is required to form functional channels. The β-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 α-interaction domain, the functional significance of the Src homology 3 domain remains elusive. Here, we show that injection of isolated β-subunit Src homology 3 domain into Xenopus laevis oocytes expressing the α1-subunit reduces the number of channels in the plasma membrane. This effect is reverted by coexpressing α1 with a dominant-negative mutant of dynamin, a GTPase involved in receptor-mediated endocytosis. Full-length β-subunit also down-regulates voltage-gated calcium channels but only when lacking the α-interaction domain. Moreover, isolated Src homology 3 domain and the full-length β-subunit were found to interact in vitro with dynamin and to internalize the distantly related Shaker potassium channel. These results demonstrate that the β-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 β-subunit to the α1-pore-forming subunit. Our findings define a novel function for the β-subunit through its Src homology 3 domain and establish a link between voltage-gated calcium channel activity and the cell endocytic machinery. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

Más información

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
Volumen: 282
Número: 4
Editorial: Elsevier
Fecha de publicación: 2007
Página de inicio: 2156
Página final: 2162
Idioma: English
URL: http://www.jbc.org/cgi/doi/10.1074/jbc.M609071200
DOI:

10.1074/jbc.M609071200

Notas: ISI, SCOPUS