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Sci Rep 2019 Nov 05;91:16049. doi: 10.1038/s41598-019-52556-0.
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Trpc1 as the Missing Link Between the Bmp and Ca2+ Signalling Pathways During Neural Specification in Amphibians.

Néant I , Leung HC , Webb SE , Miller AL , Moreau M , Leclerc C .

In amphibians, the inhibition of bone morphogenetic protein (BMP) in the dorsal ectoderm has been proposed to be responsible for the first step of neural specification, called neural induction. We previously demonstrated that in Xenopus laevis embryos, the BMP signalling antagonist, noggin, triggers an influx of Ca2+ through voltage-dependent L-type Ca2+ channels (LTCCs), mainly via CaV1.2, and we showed that this influx constitutes a necessary and sufficient signal for triggering the expression of neural genes. However, the mechanism linking the inhibition of BMP signalling with the activation of LTCCs remained unknown. Here, we demonstrate that the transient receptor potential canonical subfamily member 1, (Trpc1), is an intermediate between BMP receptor type II (BMPRII) and the CaV1.2 channel. We show that noggin induces a physical interaction between BMPRII and Trpc1 channels. This interaction leads to the activation of Trpc1 channels and to an influx of cations, which depolarizes the plasma membrane up to a threshold sufficient to activate Cav1.2. Together, our results demonstrate for the first time that during neural induction, Ca2+ entry through the CaV1.2 channel results from the noggin-induced interaction between Trpc1 and BMPRII.

PubMed ID: 31690785
PMC ID: PMC6831629
Article link: Sci Rep
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: bmp4 bmpr2 cacna1c cacna1d cacna1f cacna1s cav1 msx1 myc nog odc1 orai1 pkd2 prmt1 rrad sox2 trpc1 trpv4 zic3
Antibodies: Trpc1 AB1
Morpholinos: trpc1 MO1 trpc1 MO3

Article Images: [+] show captions
References [+] :
Ambudkar, TRPC1, Orai1, and STIM1 in SOCE: Friends in tight spaces. 2017, Pubmed