Dying cells, dyeing channels, and seasonal changes in neurotransmitter identity

This month's installment of Generally Physiological concerns signals from apoptotic cells that promote muscle development, food dyes that selectively block the pannexin 1 (Panx1) ATP channel, and photoperiod-dependent switches in neurotransmit-ter phenotype. The multinucleated myofibers that make up muscle are generated through the fusion of mononuclear myoblasts. Noting that a signaling module (ELMO-Dock180-Rac1) that promotes engulfment of apoptotic cells by phagocytes has been implicated in myoblast fusion, Hochreiter-Hufford et al. (2013) identified a role in myogenesis for signals from apop-totic cells. During apoptosis, phos-phoserine, which typically localizes to the inner leaflet of the plasma membrane, becomes exposed on the cell surface; the exposed phospho-serine acts as a ligand for the receptor BAI1, initiating the ELMO-Dock180-Rac1 pathway in phagocytes to facilitate the clearance of apoptotic cells (see Yu and Baylies, 2013). After determining that BAI1 was also present in developing myofibers and cultured myoblasts—increasing in abundance in the latter during fusion—Hochreiter-Hufford et al. (2013) showed that its overexpression increased both myotube number and the number of nuclei per myotube, effects that depended on signaling through the ELMO-Dock180-Rac1 module. Apoptotic cells were present in developing myofibers as well as in cultures in which myoblasts were undergoing fusion; in vitro analyses indicated that inhibiting apoptosis (or masking phosphoserine) inhibited myoblast fusion, whereas adding apop totic cells promoted it. Intriguingly , apoptotic myoblasts stimulated myoblast fusion but did not appear to undergo fusion themselves. The muscles of transgenic mice lacking BAI1 were smaller than those of wild-type mice; moreover, their regen-eration after injury was impaired. Thus, apoptotic cells appear to signal through the phosphoserine receptor BAI1 to promote myoblast fusion during both muscle development and muscle repair. Dyeing to inhibit ATP release? Panx1, which is found in numerous cell and tissue types, forms plasma membrane channels that mediate the release of ATP. Panx1 can interact with the P2X7 purinergic receptor (P2X7R), where it may act to enhance the local concentration of ligand. Both P2X7R and Panx1 have ATP-binding sites, and, intriguingly, various P2X7R agonists and antagonists inhibit Panx1. However, the lack of specific inhibitors for Panx1 has been a barrier in dissecting the physiological contributions of the two receptors. Moreover, given the implication of Panx1 in a range of diseases , the identification of selective inhibitors could prove therapeutically useful. Wang et al. (2013) discovered that the food dye Brilliant Blue FCF (BB FCF; also known as FD&C Blue No. 1) and the related …