Lipid raft-dependent endocytosis of close homolog of adhesion molecule L1 (CHL1) promotes neuritogenesis.
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Lipid raft-dependent endocytosis of close homolog of adhesion molecule L1 (CHL1) promotes neuritogenesis. / Tian, Nan; Leshchyns´ka, Iryna; Welch, Jeffrey H; Diakowski, Witold; Yang, Hongyuan; Schachner, Melitta; Sytnyk, Vladimir.
in: J BIOL CHEM, Jahrgang 287, Nr. 53, 53, 2012, S. 44447-44463.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Lipid raft-dependent endocytosis of close homolog of adhesion molecule L1 (CHL1) promotes neuritogenesis.
AU - Tian, Nan
AU - Leshchyns´ka, Iryna
AU - Welch, Jeffrey H
AU - Diakowski, Witold
AU - Yang, Hongyuan
AU - Schachner, Melitta
AU - Sytnyk, Vladimir
PY - 2012
Y1 - 2012
N2 - 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 ?II spectrin as a binding partner of CHL1, and we show that partial disruption of the complex between CHL1 and ?II 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-?II spectrin complex and CHL1 endocytosis are required for CHL1-dependent neurite outgrowth.
AB - 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 ?II spectrin as a binding partner of CHL1, and we show that partial disruption of the complex between CHL1 and ?II 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-?II spectrin complex and CHL1 endocytosis are required for CHL1-dependent neurite outgrowth.
KW - Animals
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Calcium/metabolism
KW - Cell Adhesion Molecules/genetics/metabolism
KW - Lipoylation
KW - Neurons/cytology/metabolism
KW - Endocytosis
KW - Neurites/metabolism
KW - Microfilament Proteins/genetics/metabolism
KW - Carrier Proteins/genetics/metabolism
KW - Cell Membrane/genetics/metabolism
KW - Membrane Lipids/metabolism
KW - Neurogenesis
KW - Animals
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Calcium/metabolism
KW - Cell Adhesion Molecules/genetics/metabolism
KW - Lipoylation
KW - Neurons/cytology/metabolism
KW - Endocytosis
KW - Neurites/metabolism
KW - Microfilament Proteins/genetics/metabolism
KW - Carrier Proteins/genetics/metabolism
KW - Cell Membrane/genetics/metabolism
KW - Membrane Lipids/metabolism
KW - Neurogenesis
M3 - SCORING: Journal article
VL - 287
SP - 44447
EP - 44463
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 53
M1 - 53
ER -
