Transmembrane agrin regulates filopodia in rat hippocampal neurons in culture.

Full Abstract

Filopodia mediate axon guidance, neurite branching and synapse formation, but the membrane molecules that regulate neuronal filopodia in response to extracellular cues are largely unknown. The transmembrane isoform of the proteoglycan agrin, expressed predominantly in the CNS, may regulate neurite outgrowth, synapse formation and excitatory signaling. Here we demonstrate that agrin positively regulates neuronal filopodia. Over-expression of TM-agrin caused the formation of excess filopodia on neurites of hippocampal neurons cultured 1-6 days. Conversely, suppression of agrin expression by siRNA reduced the number of filopodia. Time lapse analysis indicated that endogenous TM-agrin regulates filopodia by increasing their stability and initiation. The N-terminal half of agrin was necessary for induction of filopodia, and over-expression of TM-agrin in a neuronal cell line increased Cdc42 activation, suggesting a role for Cdc42 downstream of agrin. By positively regulating filopodia in developing neurons, TM-agrin may influence the pattern of neurite outgrowth and synapse formation.

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Author information

Author/s: McCroskery, Seumas (S); Chaudhry, Amal (A); Lin, Lin (L); Daniels, Mathew P (MP);

Affiliation: Laboratory of Cell Biology, National Heart Lung and Blood Institute, NIH, 50 South Drive, Bldg. 50, Rm 3318, Bethesda, MD 20892, USA.

Journal and publication information

Publication Type: Journal Article

Journal: Molecular and cellular neurosciences (Mol Cell Neurosci), published in United States. (Language: eng)

Reference: 2006-Sep; vol 33 (issue 1) : pp 15-28

Dates: Created 2006/09/01; Completed 2007/04/30;

PMID: 16860570, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Agrin - genetics; metabolism
Animals
Cell Line
Cell Membrane - metabolism
Cells, Cultured
Enzyme Activation
Hippocampus - cytology

Hippocampus - cytology
Neurons - cytology; metabolism; ultrastructure
Pseudopodia - metabolism; ultrastructure
RNA, Small Interfering - genetics; metabolism
Rats
Transfection
cdc42 GTP-Binding Protein - genetics; metabolism

Associated Chemicals: Agrin (0) ; RNA, Small Interfering (0) ; cdc42 GTP-Binding Protein (EC 3.6.5.2)

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