Calcium-sensing mechanism in TRPC5 channels contributing to retardation of neurite outgrowth.
The calcium- and sodium-permeable transient receptor potential channel TRPC5 has an inhibitory role in neuronal outgrowth but the mechanisms governing its activity are poorly understood. Here we propose a mechanism involving the neuronal calcium sensor-1 (NCS-1) protein. Inhibitory mutants of TRPC5 and NCS-1 enhance neurite outgrowth similarly. Mutant NCS-1 does not inhibit surface-expression of TRPC5 but generally suppresses channel activity, irrespective of whether it is evoked by carbachol, store depletion, lanthanides or elevated intracellular calcium. NCS-1 and TRPC5 are in the same protein complex in rat brain and NCS-1 directly binds to the TRPC5 C-terminus. The data suggest protein-protein interaction between NCS-1 and TRPC5, and involvement of this protein complex in retardation of neurite outgrowth.
Hui
Hui
H
Institute of Membrane and Systems Biology, Garstang Building, University of Leeds, Leeds LS2 9JT, UK.
McHugh
Damian
D
Hannan
Meredith
M
Zeng
Fanning
F
Xu
Shang-Zhong
SZ
Khan
Saeed-Ul-Hassan
SU
Levenson
Robert
R
Beech
David J
DJ
Weiss
Jamie L
JL
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D049108:Cell Enlargement; D002460:Cell Line; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D051580:Neuronal Calcium-Sensor Proteins; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D050052:TRPC Cation Channels / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D050052:TRPC Cation Channels; C112021:Trpc5 protein, mouse; C101464:frequenin calcium sensor proteins; D002118:Calcium