Kinesin-1 promotes post-Golgi trafficking of NCAM140 and NCAM180 to the cell surface

The neural cell adhesion molecule (NCAM, also known as NCAM1) is important during neural development, because it contributes to neurite outgrowth in response to its ligands at the cell surface. In the adult brain, NCAM is involved in regulating synaptic plasticity. The molecular mechanisms underlying delivery of NCAM to the neuronal cell surface remain poorly understood. We used a protein macroarray and identified the kinesin light chain 1 (KLC1), a component of the kinesin-1 motor protein, as a binding partner of the intracellular domains of the two transmembrane isoforms of NCAM, NCAM140 and NCAM180. KLC1 binds to amino acids CGKAGPGA within the intracellular domain of NCAM and colocalizes with kinesin-1 in the Golgi compartment. Delivery of NCAM180 to the cell surface is increased in CHO cells and neurons co-transfected with kinesin-1. We further demonstrate that the p21-activated kinase 1 (PAK1) competes with KLC1 for binding to the intracellular domain of NCAM and contributes to the regulation of the membrane insertion of NCAM. Our results indicate that NCAM is delivered to the cell surface through a kinesin-1-mediated transport mechanism in a PAK1-dependent manner.