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Transmembrane agrin regulates filopodia in rat hippocampal neurons in culture.
- Source :
-
Molecular and cellular neurosciences [Mol Cell Neurosci] 2006 Sep; Vol. 33 (1), pp. 15-28. Date of Electronic Publication: 2006 Jul 24. - Publication Year :
- 2006
-
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.
- Subjects :
- Agrin genetics
Animals
Cell Line
Cells, Cultured
Enzyme Activation
Neurons cytology
Pseudopodia ultrastructure
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Rats
Transfection
cdc42 GTP-Binding Protein genetics
cdc42 GTP-Binding Protein metabolism
Agrin metabolism
Cell Membrane metabolism
Hippocampus cytology
Neurons metabolism
Neurons ultrastructure
Pseudopodia metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1044-7431
- Volume :
- 33
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular and cellular neurosciences
- Publication Type :
- Academic Journal
- Accession number :
- 16860570
- Full Text :
- https://doi.org/10.1016/j.mcn.2006.06.004