Na+ channel β subunits: overachievers of the ion channel family

They talk about helping migration, a useful thing to understand about neurogenesis
http://www.frontiersin.org/Journal/FullText.aspx?ART_DOI=10.3389/fphar.2011.00053&name=pharmacology_of_ion_channels_and_channelopathies

Voltage-gated Na⁺ channels (VGSCs) in mammals contain a pore-forming α subunit and one or more β subunits. There are five mammalian β subunits in total: β1, β1B, β2, β3, and β4, encoded by four genes: SCN1B–SCN4B. With the exception of the SCN1B splice variant, β1B, the β subunits are type I topology transmembrane proteins. In contrast, β1B lacks a transmembrane domain and is a secreted protein. A growing body of work shows that VGSC β subunits are multifunctional. While they do not form the ion channel pore, β subunits alter gating, voltage-dependence, and kinetics of VGSCα subunits and thus regulate cellular excitability in vivo. In addition to their roles in channel modulation, β subunits are members of the immunoglobulin superfamily of cell adhesion molecules and regulate cell adhesion and migration. β subunits are also substrates for sequential proteolytic cleavage by secretases. An example of the multifunctional nature of β subunits is β1, encoded by SCN1B, that plays a critical role in neuronal migration and pathfinding during brain development, and whose function is dependent on Na⁺ current and γ-secretase activity. Functional deletion of SCN1B results in Dravet Syndrome, a severe and intractable pediatric epileptic encephalopathy. β subunits are emerging as key players in a wide variety of physiopathologies, including epilepsy, cardiac arrhythmia, multiple sclerosis, Huntington’s disease, neuropsychiatric disorders, neuropathic and inflammatory pain, and cancer. β subunits mediate multiple signaling pathways on different timescales, regulating electrical excitability, adhesion, migration, pathfinding, and transcription. Importantly, some β subunit functions may operate independently of α subunits. Thus, β subunits perform critical roles during development and disease. As such, they may prove useful in disease diagnosis and therapy.

Introduction

Mammalian voltage-gated Na⁺ channels (VGSCs) exist as macromolecular complexes in vivo, comprising, at minimum, one pore-forming α subunit and one or more β subunits in a 1:1 stoichiometry for α:β (Catterall, 1992). Traditionally, VGSC β subunits have been termed “auxiliary.” However, increasing evidence suggests that the β subunits are far from auxiliary, and, in fact, function as critical signaling molecules in their own right, perhaps even independently of α subunits. In this review, we will summarize the latest developments describing the growing, diverse, multifunctional roles of the β subunits, including their contribution to human disease