title: Lipid raft-dependent endocytosis of close homolog of adhesion molecule L1 (CHL1) promotes neuritogenesis.
abstract: CHL1 plays a dual role by either promoting or inhibiting neuritogenesis. We report here that neuritogenesis-promoting ligand-dependent cell surface clustering of CHL1 induces palmitoylation and lipid raft-dependent endocytosis of CHL1. We identify βII spectrin as a binding partner of CHL1, and we show that partial disruption of the complex between CHL1 and βII spectrin accompanies CHL1 endocytosis. Inhibition of the association of CHL1 with lipid rafts by pharmacological disruption of lipid rafts or by mutation of cysteine 1102 within the intracellular domain of CHL1 reduces endocytosis of CHL1. Endocytosis of CHL1 is also reduced by nifedipine, an inhibitor of the L-type voltage-dependent Ca(2+) channels. CHL1-dependent neurite outgrowth is reduced by inhibitors of lipid raft assembly, inhibitors of voltage-dependent Ca(2+) channels, and overexpression of CHL1 with mutated cysteine Cys-1102. Our results suggest that ligand-induced and lipid raft-dependent regulation of CHL1 adhesion via Ca(2+)-dependent remodeling of the CHL1-βII spectrin complex and CHL1 endocytosis are required for CHL1-dependent neurite outgrowth.
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universitätskrankenhaus Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Nan
authors.initials: N
authors.lastname: Tian
authors.forename: Iryna
authors.initials: I
authors.lastname: Leshchyns'ka
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Welch
authors.forename: Witold
authors.initials: W
authors.lastname: Diakowski
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Yang
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sytnyk
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis; D054878:Lipoylation; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D013049:Spectrin
chemical_list: D002118:Calcium; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D008563:Membrane Lipids; D008840:Microfilament Proteins; D013049:Spectrin; C490649:Chl1 protein, mouse