TRPC5 is a regulator of hippocampal neurite length and growth cone morphology.
Growth cone motility is regulated by both fast voltage-dependent Ca2+ channels and by unknown receptor-operated Ca2+ entry mechanisms. Transient receptor potential (TRP) homomeric TRPC5 ion channels are receptor-operated, Ca2+-permeable channels predominantly expressed in the brain. Here we show that TRPC5 is expressed in growth cones of young rat hippocampal neurons. Our results indicate that TRPC5 channel subunits interact with the growth cone-enriched protein stathmin 2, are packaged into vesicles and are carried to newly forming growth cones and synapses. Once in the growth cone, TRPC5 channels regulate neurite extension and growth-cone morphology. Dominant-negative TRPC5 expression allowed significantly longer neurites and filopodia to form. We conclude that TRPC5 channels are important components of the mechanism controlling neurite extension and growth cone morphology.
Greka
Anna
A
Howard Hughes Medical Institute, Children's Hospital and Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
Navarro
Betsy
B
Oancea
Elena
E
Duggan
Anne
A
Clapham
David E
DE
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D027682:Cation Transport Proteins; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004553:Electric Conductivity; D020439:Growth Cones / Q000648:ultrastructure*; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure*; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D008868:Microtubule Proteins; D016501:Neurites / Q000648:ultrastructure*; D009474:Neurons / Q000378:metabolism; D010750:Phosphoproteins / Q000502:physiology; D020033:Protein Isoforms / Q000502:physiology; D051381:Rats; D050777:Stathmin; D050052:TRPC Cation Channels
D015220:Calcium Channels; D027682:Cation Transport Proteins; D008868:Microtubule Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D050777:Stathmin; D050052:TRPC Cation Channels; C503500:Trpc5 protein, rat