J Neurosci. 2005 Mar 9;25(10):2687-701.

Canonical transient receptor potential 1 plays a role in basic fibroblast growth factor (bFGF)/FGF receptor-1-induced Ca2+ entry and embryonic rat neural stem cell proliferation.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Fiorio Pla, A., Maric, D., Brazer, S. C., Giacobini, P., Liu, X., Chang, Y. H., Ambudkar, I. S., Barker, J. L.,
["Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. alessandra.fiorio@unito.it"]
Basic fibroblast growth factor (bFGF) and its major receptor FGF receptor-1 (FGFR-1) play an important role in the development of the cortex. The mechanisms underlying the mitogenic role of bFGF/FGFR-1 signaling have not been elucidated. Intracellular Ca2+ concentrations ([Ca2+]i) in proliferating cortical neuroepithelial cells are markedly dependent on Ca2+ entry (Maric et al., 2000a). The absence of voltage-dependent Ca2+ entry channels, which emerge later, indicates that other membrane mechanisms regulate [Ca2+]i during proliferation. Canonical transient receptor potential (TRPC) family channels are candidates because they are voltage independent and are expressed during CNS development (Strubing et al., 2003). Here, we investigated the involvement of TRPC1 in bFGF-mediated Ca2+ entry and proliferation of embryonic rat neural stem cells (NSCs). Both TRPC1 and FGFR-1 are expressed in the embryonic rat telencephalon and coimmunoprecipitate. Quantitative fluorescence-activated cell sorting analyses of phenotyped telencephalic dissociates show that approximately 80% of NSCs are TRPC1+, proliferating, and express FGFR-1. Like NSCs profiled ex vivo, NSC-derived progeny proliferating in vitro coexpress TRPC1 and FGFR1. Antisense knock-down of TRPC1 significantly decreases bFGF-mediated proliferation of NSC progeny, reduces the Ca2+ entry component of the Cai2+ response to bFGF without affecting Ca2+ release from intracellular stores or 1-oleoyl-2-acetyl-sn-glycerol-induced Ca2+ entry, and significantly blocks an inward cation current evoked by bFGF in proliferating NSCs. Both Ca2+ influx evoked by bFGF and NSC proliferation are attenuated by Gd3+ and SKF96365 two antagonists of agonist-stimulated Ca2+ entry. Together, these results show that TRPC1 contributes to bFGF/FGFR-1-induced Ca2+ influx, which is involved in self-renewal of embryonic rat NSCs.
PMID: 15758179External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Screening Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 FGFR-1 Inference Prediction 15758179
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 FGFR-1 Co-immunoprecipitation Rat telencephalon 15758179
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 FGFR-1 Co-immunofluorescence staining Rat neural stem cell 15758179
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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