Leftward transfer of a chemosensory polycystin initiates left-dominant calcium signaling for lateralized embryonic development

Abstract

Left-dominant [Ca2+]ielevation on the margin of ventral node furnishes the initial laterality signaling in mouse embryos. It depends on nodal flow, FGFR signaling, and PKD1L1-containing polycystin channels, of which interrelationship is still missing. Here we show that PKD1L1 protein is predominantly accumulated on the left margin of the nodal pit and serves as a chemosensory channel for Nodal-mediated [Ca2+]ielevation. PKD1L1/PKD2 overexpression augmented the Nodal sensitivity of fibroblasts. We detected PKD1L1-containing fragile meshwork of fibrous strands in KikGR-PKD1L1 knockin mice, especially when extraembryonic membrane was preserved. The portion of meshwork bridging over nodal crown cells significantly lateralized to the left. This bridge was formed by a leftward flow of PKD1L1-containing fibrous strands, which can be suppressed by the FGFR inhibitor SU5402 that antagonized the [Ca2+]ielevation as well. These data provide evidence for a leftward transfer of chemosensory PKD1L1 polycystin channel, as a readout mechanism of nodal flow.

Kinesin-1 mediates proper ER folding of the CaV1.2 channel and maintains mouse glucose homeostasis

“…For the BFA washout assay, the cells were transduced with a rabbit Ca v 1.2-EGFP expression vector (Navedo et al ., 2010) in the presence of 1 μM brefeldin A (Sigma Aldrich) at 19.5°C overnight. Then, the cells were washed out using complete medium twice, cultured at 37°C for the indicated times, and subjected to confocal laser scanning microscopy as described previously (Nakata & Hirokawa, 2003; Tanaka et al ., 2023).…”