Linked Life Data

12077189

Source:http://linkedlifedata.com/resource/pubmed/id/12077189

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2002-6-21
pubmed:abstractText
The L1 adhesion molecule regulates axon growth and is mutated in the X-linked mental retardation syndrome CRASH (acronym for corpus callosum agenesis, retardation, aphasia, spastic paraplegia, hydrocephalus). A novel role for L1 as a potentiator of neuronal cell migration to extracellular matrix proteins through beta1 integrins and intracellular signaling to mitogen-activated protein (MAP) kinase was identified. L1 potentiated haptotactic migration of B35 neuroblastoma cells toward fibronectin, vitronectin, and laminin through the signaling intermediates c-Src, phosphatidylinositol-3 kinase, and MAP kinase. L1 potentiated migration toward fibronectin through alpha5beta1 integrin in human embryonic kidney 293 cells and depended on determinants of L1 endocytosis: dynamin I, c-Src, and the AP2/clathrin binding site (Arg-Ser-Leu-Glu) in the neuronal splice form of L1. L1 clustering on the cell surface enhanced the internalization of activated beta1 integrins and L1 into distinct endocytic vesicles. L1-potentiated migration, enhancement of beta1 integrin endocytosis, and activation of MAP kinase were coordinately inhibited by mutation of an RGD sequence in the sixth immunoglobulin-like domain of L1. Moreover, three CRASH mutations in the L1 cytoplasmic domain (1194L, S1224L, Y1229H), two of which interfere with ankyrin association, inhibited L1-potentiated migration and MAP kinase activation. Function-blocking antibodies to L1 and beta1 integrin retarded the migration of 5-bromo-2'-deoxyuridine-labeled mouse cerebellar granule cells in slice cultures, underscoring the potential physiological relevance of these findings. These studies suggest that L1 functionally interacts with beta1 integrins to potentiate neuronal migration toward extracellular matrix proteins through endocytosis and MAP kinase signaling, and that impairment of this function by L1 cytoplasmic domain mutations may contribute to neurological deficits in CRASH.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4918-31
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12077189-Animals, pubmed-meshheading:12077189-Antibodies, pubmed-meshheading:12077189-Antigens, CD29, pubmed-meshheading:12077189-Cell Line, pubmed-meshheading:12077189-Cell Movement, pubmed-meshheading:12077189-Cerebellum, pubmed-meshheading:12077189-Endocytosis, pubmed-meshheading:12077189-Extracellular Matrix Proteins, pubmed-meshheading:12077189-Humans, pubmed-meshheading:12077189-Integrins, pubmed-meshheading:12077189-Leukocyte L1 Antigen Complex, pubmed-meshheading:12077189-MAP Kinase Signaling System, pubmed-meshheading:12077189-Membrane Glycoproteins, pubmed-meshheading:12077189-Mice, pubmed-meshheading:12077189-Mutation, pubmed-meshheading:12077189-Neural Cell Adhesion Molecules, pubmed-meshheading:12077189-Neurons, pubmed-meshheading:12077189-Oligopeptides, pubmed-meshheading:12077189-Protein Structure, Tertiary, pubmed-meshheading:12077189-Rats, pubmed-meshheading:12077189-Tumor Cells, Cultured
pubmed:year
2002
pubmed:articleTitle
The neural cell adhesion molecule L1 potentiates integrin-dependent cell migration to extracellular matrix proteins.
pubmed:affiliation
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.