The Ca2+-independent neuronal cell adhesion molecules (NCAMs) are cell surface proteins that are integral to the development of the nervous system and necessary for maintaining synaptic plasticity in the adult brain. Two major NCAM splice variants, NCAM140 and NCAM180, have transmembrane and intracellular domains, and although their function depends on their efficient transport to the cell surface, the mechanisms of that process are unclear. Here (p. ), Vladimir Sytnyk and colleagues identified kinesin light chain 1 (KLC1) as a new binding partner for the NCAM intracellular domain, and investigated the role this interaction plays in NCAM trafficking. KLC1 colocalised with NCAMs inside neurites and neuronal cell bodies, predominantly in the trans-Golgi compartment. Importantly, in Chinese hamster ovary cells and cultured mouse cortical neurons, kinesin-1 binding to NCAM180 promoted delivery of NCAM180 to the cell surface. The authors also demonstrated that kinesin-1-dependent NCAM cell surface delivery is regulated by p21-activated kinase (PAK1) because it competes with kinesin-1 for the NCAM-binding site. In addition, they found that submembrane NCAM regions, which can interact with components of the exocyst complex, are also important for kinesin-1-dependent cell surface targeting. Taken together, these data significantly advance our knowledge of basic NCAM biology by demonstrating that kinesin-1 functions in post-trans-Golgi trafficking of NCAMs to the cell surface in a PAK1-regulated manner.
