title: Kinesin-1 promotes post-Golgi trafficking of NCAM140 and NCAM180 to the cell surface.
abstract: 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.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia Institute of Nutrition and Food Science, Department of Human Metabolomics, University of Bonn, Bonn 53115, Germany.
authors.forename: Hilke
authors.initials: H
authors.lastname: Wobst
authors.affiliation: Institute of Nutrition and Food Science, Department of Human Metabolomics, University of Bonn, Bonn 53115, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schmitz
authors.affiliation: Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854-8082, USA Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.affiliation: Institute of Nutrition and Food Science, Department of Human Metabolomics, University of Bonn, Bonn 53115, Germany s.diestel@uni-bonn.de iryna.leshchynska@unsw.edu.au v.sytnyk@unsw.edu.au.
authors.forename: Simone
authors.initials: S
authors.lastname: Diestel
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia s.diestel@uni-bonn.de iryna.leshchynska@unsw.edu.au v.sytnyk@unsw.edu.au.
authors.forename: Iryna
authors.initials: I
authors.lastname: Leshchyns'ka
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia s.diestel@uni-bonn.de iryna.leshchynska@unsw.edu.au v.sytnyk@unsw.edu.au.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sytnyk
mesh_terms: D000818:Animals; D016466:CHO Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003412:Cricetulus; D006056:Golgi Apparatus / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C000715688:KLC1 protein, human; C000715695:Kns2 protein, mouse; C520249:NCAM140, human; D034741:RNA, Small Interfering; C515905:Pak1 protein, mouse; D054462:p21-Activated Kinases; C475469:Kif5b protein, mouse; D016547:Kinesins
keywords: Cell adhesion molecule; Cell surface delivery; Neurons