In the context of cell migration, it has a paradoxical role in that global inhibition or activation of PKA inhibits migration. Protein Kinase A (PKA) is a ubiquitous serine/threonine kinase involved in innumerable cellular processes. Thus, the signaling proteins that regulate these various structural processes must also be distinctly regulated in subcellular space. Importantly, all of the aforementioned channels have been shown to be either direct substrates of PKA or regulated downstream of PKA activity (TRPM7 (Takezawa et al., 2004), establishing these and possibly other members of the TRP channel family as important players in PKA-mediated ion flux during migration.Ĭell migration requires establishment and maintenance of directional polarity, which in turn requires spatial heterogeneity in the regulation of protrusion, retraction, and adhesion. Transient Receptor Potential (TRP) channels, particularly TRPC6 (Weber et al., 2015 Farmer et al., 2019 Asghar and Törnquist, 2020), TRPV1 (Miyake et al., 2015), TRPV4 (Mrkonjić et al., 2015 Li et al., 2020 Yang et al., 2020 Lakk and Križaj, 2021), and TRPM7 (Clark et al., 2006 Su et al., 2006 Wei et al., 2009 Wang et al., 2014 Broertjes et al., 2019 Lefebvre et al., 2020 Yankaskas et al., 2021) are increasingly recognized as important regulators of cellular migration, as thoughtfully reviewed in (Howe, 2011 Fiorio Pla and Gkika, 2013 Canales et al., 2019).

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