The mechanosensitive channel Piezo1 cooperates with semaphorins to control neural crest migration

Abstract

Cells are permanently exposed to a multitude of different kinds of signals: however, how cells respond to simultaneous extracellular signals within a complex in vivo environment is poorly understood. Here, we studied the role of the mechanosensitive ion channel Piezo1 on the migration of the neural crest, a multipotent embryonic cell population. We identify that Piezo1 is required for the migration of Xenopus cephalic neural crest. We show that loss of Piezo1 promotes focal adhesion turnover and cytoskeletal dynamics by controlling Rac1 activity, leading to increased speed of migration. Moreover, overactivation of Rac1, due to Piezo1 inhibition, counteracts cell migration inhibitory signals by Semaphorin 3A and Semaphorin 3F, generating aberrant neural crest invasion in vivo. Thus, we find that, for directional migration in vivo, neural crest cells require a tight regulation of Rac1, by semaphorins and Piezo1. We reveal here that a balance between a myriad of signals through Rac1 dictates cell migration in vivo, a mechanism that is likely to be conserved in other cell migration processes.

Protein Kinase A in cellular migration—Niche signaling of a ubiquitous kinase

“…Piezo channels are massive, mechanically sensitive ion channels known to transmit mechanical signals, activate integrins, and regulate cell migration in several ways ( Gottlieb, 2017 ; Nourse and Pathak, 2017 ; Canales Coutino and Mayor, 2021 ; Dombroski et al, 2021 ; Holt et al, 2021 ). PKA activity is potentiated by calcium influx downstream of piezo1 in confined migration ( Hung et al, 2016 ) and piezo2 activity is enhanced by increased PKA activity ( Dubin et al, 2012 ), suggesting a link between PKA and piezo channels in migration.…”

Guidance by followers ensures long-range coordination of cell migration through α-catenin mechanoperception

“…While chemoattraction is the best characterized guidance mechanism, some cells rely on mechanical signals for their guidance (Roca-Cusachs et al, 2013). In durotaxis, cells follow gradients in the stiffness of their substrate (Lo et al, 2000;SenGupta et al, 2021;Shellard and Mayor, 2020), a process recently observed in the embryo (Canales Coutiño and Mayor, 2021;Shellard and Mayor, 2021). In addition to following gradients in matrix stiffness, it has been proposed that cells can be guided by physical forces applied at cell-cell contacts (Cai et al, 2014;Tambe et al, 2011).…”

Migrating neurons adapt motility modes to brain microenvironments via a mechanosensor, PIEZO1

“…4F). Piezo1 has been implicated in actin remodeling during cell migration, but its role in the rear-biased actomyosin contraction in 3D migration has not been reported ( 16, 31, 32 ). Notably, ezrin translocation was strongly biased to the posterior membrane by bath-applied Yoda1 in nonconfined spaces, suggesting that asymmetric shape and/or molecular distribution in the polarized neuron also contribute to local activation of ezrin and actomyosin at the cell rear ( 2 ).…”