title: Migration of nerve growth cones requires detergent-resistant membranes in a spatially defined and substrate-dependent manner.
abstract: Motility of nerve growth cones (GCs) is regulated by region-specific activities of cell adhesion molecules (CAMs). CAM activities could be modified by their localization to detergent-resistant membranes (DRMs), specialized microdomains enriched in signaling molecules. This paper deals with a question of whether DRMs are involved in GC migration stimulated by three CAMs; L1, N-cadherin (Ncad), and beta1 integrin. We demonstrate that L1 and Ncad are present in DRMs, whereas beta1 integrin is exclusively detected in non-DRMs of neurons and that localization of L1 and Ncad to DRMs is developmentally regulated. GC migration mediated by L1 and Ncad but not by beta1 integrin is inhibited after DRM disruption by micro-scale chromophore-assisted laser inactivation (micro-CALI) of GM1 gangliosides or by pharmacological treatments that deplete cellular cholesterol or sphingolipids, essential components for DRMs. Characteristic morphology of GCs induced by L1 and Ncad is also affected by micro-CALI-mediated DRM disruption. Micro-CALI within the peripheral domain of GCs, or even within smaller areas such as the filopodia and the lamellipodia, is sufficient to impair their migration. However, micro-CALI within the central domain does not affect GC migration. These results demonstrate the region-specific involvement of DRMs in CAM-dependent GC behavior.
authors.affiliation: Developmental Brain Science Group, RIKEN Brain Science Institute (BSI), Wako, Saitama, 351-0198, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamiguchi
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology*; D004351:Drug Resistance; D005677:G(M1) Ganglioside / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013107:Sphingolipids / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000378:metabolism
chemical_list: D015820:Cadherins; D003902:Detergents; D019012:Integrin beta1; D013107:Sphingolipids; D014759:Viral Envelope Proteins; C076634:NEG envelope glycoprotein, Negishi virus; D005677:G(M1) Ganglioside; D002784:Cholesterol