tailieunhanh - Báo cáo khoa học: TRPV1 at nerve endings regulates growth cone morphology and movement through cytoskeleton reorganization

While the importance of Ca2+ channel activity in axonal path finding is established, the underlying mechanisms are not clear. Here, we show that transient receptor potential vanilloid receptor 1 (TRPV1), a member of the TRP superfamily of nonspecific ion channels, is physically and functionally present at dynamic neuronal extensions, including growth cones. | ễFEBS Journal TRPV1 at nerve endings regulates growth cone morphology and movement through cytoskeleton reorganization C. Goswami1 z H. Schmidt2 and F. Hucho1 1 Freie Universitat Berlin Institut fur Chemie und Biochemie Berlin Germany 2 Department of DevelopmentalNeurobiology Max Delbruck Centrum for Molecular Medicine Berlin Germany Keywords capsaicin cytoskeleton dorsal root ganglia DRG growth cone TRPV1 Correspondence F. Hucho Freie Universitat Berlin Institut fur Chemie und Biochemie Thielallee 63 14195 Berlin Germany Fax 49 30 83853753 Tel 49 30 83855545 E-mail hucho@ C. Goswami Department of Human Molecular Genetics Max Planck Institute for Molecular Genetics Ihnestrasse 63-73 14195 Berlin Germany Fax 49 30 84131383 Tel 49 30 84131243 E-mail goswami@ Present address Department of Human Molecular Genetics Max Planck Institute for Molecular Genetics Berlin Germany Received 19 August 2006 revised 29 September 2006 accepted 1 December 2006 doi While the importance of Ca2 channel activity in axonal path finding is established the underlying mechanisms are not clear. Here we show that transient receptor potential vanilloid receptor 1 TRPV1 a member of the TRP superfamily of nonspecific ion channels is physically and functionally present at dynamic neuronal extensions including growth cones. These nonselective cation channels sense exogenous ligands such as resenifera toxin and endogenous ligands such as N-arachidonoyl-dopamine NADA and affect the integrity of microtubule cytoskeleton. Using TRPV1-transiently transfected F11 cells and embryonic dorsal root ganglia explants we show that activation of TRPV1 results in growth cone retraction and collapse and formation of varicosities along neurites. These changes were due to TRPV1-activation-mediated disassembly of microtubules and are partly Ca2 -independent. Prolonged activation with very low doses 1 nM of NADA results in shortening of neurites in the .

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