C-Terminal region of teneurin-1 co-localizes with dystroglycan and modulates cytoskeletal organization through an extracellular signal-regulated kinase-dependent stathmin- and filamin A-mediated mechanism in hippocampal cells.
The pyramidal neurons in the hippocampus are extremely neuroplastic, and the complexity of dendritic branches can be dynamically altered in response to a variety of stimuli, including learning and stress. Recently, the teneurin family of proteins has emerged as an interneuronal and extracellular matrix signaling system that plays a significant role in brain development and neuronal communication. Encoded on the last exon of the teneurin genes is a new family of bioactive peptides termed the teneurin C-terminal-associated peptides (TCAPs). Previous studies indicate that TCAP-1 regulates axon fasciculation and dendritic morphology in the hippocampus. This study was aimed at understanding the molecular mechanisms by which TCAP-1 regulates these changes in the mouse hippocampus. Fluoresceinisothiocyanate (FITC)-labeled TCAP-1 binds to the pyramidal neurons of the CA2 and CA3, and dentate gyrus in the hippocampus of the mouse brain. Moreover, FITC-TCAP-1 co-localizes with β-dystroglycan upon binding to the plasma membrane of cultured immortalized mouse E14 hippocampal cells. In culture, TCAP-1 stimulates ERK1/2-dependent phosphorylation of the cytoskeletal regulatory proteins, stathmin at serine-25 and filamin A at serine-2152. In addition, TCAP-1 induces actin polymerization, increases immunoreactivity of tubulin-based cytoskeletal elements and causes a corresponding increase in filopodia formation and mean filopodia length in cultured hippocampal cells. We postulate that the TCAP-1 region of teneurin-1 has a direct action on the cytoskeletal reorganization that precedes neurite and process development in hippocampal neurons. Our data provides novel evidence that functionally links the teneurin and dystroglycan systems and provides new insight into the molecular mechanisms by which TCAP-1 regulates cytoskeletal dynamics in hippocampal neurons. The TCAP-dystroglycan system may represent a novel mechanism associated with the regulation of hippocampal-function.
Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON, Canada M5S 3G5. dhan.chand@utoronto.ca
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D
Chand
L
L
Song
L
L
deLannoy
D
D
Barsyte-Lovejoy
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S
Ackloo
P C
PC
Boutros
K
K
Evans
D D
DD
Belsham
D A
DA
Lovejoy
D000818:Animals; D015153:Blotting, Western; D003285:Contractile Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D049030:Dystroglycans / Q000378:metabolism*; D064448:Filamins; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D017966:Pyramidal Cells / Q000378:metabolism*; D050777:Stathmin / Q000378:metabolism*; D019063:Tenascin / Q000378:metabolism*
D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D050777:Stathmin; D019063:Tenascin; C120530:teneurin-1; D049030:Dystroglycans