Sodium channel beta subunits mediate homophilic cell adhesion and recruit ankyrin to points of cell-cell contact.
Sodium channels isolated from mammalian brain are composed of alpha, beta1, and beta2 subunits. The auxiliary beta subunits do not form the ion conducting pore, yet play important roles in channel modulation and plasma membrane expression. beta1 and beta2 are transmembrane proteins with one extracellular V-set immunoglobulin (Ig) protein domain. It has been shown recently that beta1 and beta2 interact with the extracellular matrix proteins tenascin-C and tenascin-R. In the present study we show that rat brain beta1 and beta2, but not alphaIIA, subunits interact in a trans-homophilic fashion, resulting in recruitment of the cytoskeletal protein ankyrin to sites of cell-cell contact in transfected Drosophila S2 cells. Whereas alphaIIA subunits expressed alone do not cause cellular aggregation, beta subunits co-expressed with alphaIIA retain the ability to adhere and recruit ankyrin. Truncated beta subunits lacking cytoplasmic domains interact homophilically to produce cell aggregation but do not recruit ankyrin. Thus, the cytoplasmic domains of beta1 and beta2 are required for cytoskeletal interactions. It is hypothesized that sodium channel beta subunits serve as a critical communication link between the extracellular and intracellular environments of the neuron and may play a role in sodium channel placement at nodes of Ranvier.
Malhotra
J D
JD
Department of Pharmacology, The University of Michigan, Ann Arbor, Michigan 48109, USA.
Kazen-Gillespie
K
K
Hortsch
M
M
Isom
L L
LL
D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002449:Cell Aggregation; D002450:Cell Communication; D004330:Drosophila; D008969:Molecular Sequence Data; D051381:Rats; D015222:Sodium Channels / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship
D017487:Ankyrins; D015815:Cell Adhesion Molecules; D015222:Sodium Channels