Editors' ChoiceCell Biology

Highlight: A tasteful conversation with atypical mitochondria at atypical synapses

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Science Signaling  08 May 2018:
Vol. 11, Issue 529, eaat5326
DOI: 10.1126/scisignal.aat5326

Atypical mitochondria produce ATP used as a neurotransmitter by type II taste cells to transduce sweet, bitter, or savory flavors.

The exocytotic release of neurotransmitters at chemical synapses is a major mode of intercellular communication in animals with nervous systems. This phylogenetically ancient signaling pathway is defined by a functional unit of three juxtaposed subcellular compartments: a focal zone of presynaptic neurotransmitter vesicle release sites, a restricted extracellular synaptic space, and a postsynaptic site of clustered neurotransmitter receptors. However, for taste perception in vertebrates, nature has evolved an atypical mode of synaptic transmission involving nonexocytotic release of ATP from presynaptic taste cells to target ionotropic P2X purinergic receptors on postsynaptic gustatory nerves. In this issue of Science Signaling, Romanov et al. have described this noncanonical chemical synapse in the sensory type II cells of mammalian taste buds. These modified epithelial cells express diverse G protein–coupled receptors for tastant molecules, which evoke sweet, bitter, or savory sensation. The synapses between type II cells and the endings of gustatory nerves retain the basic tripartite juxtaposition of subcellular compartments but with atypical structure and function of the proximal presynaptic compartment. Although ATP can be packaged within neurosecretory vesicles for exocytotic release, type II cells lack such vesicles and the SNARE-dependent machinery for Ca2+-dependent exocytosis. Several types of large-pore ion channels can mediate the gated efflux of cytosolic ATP into extracellular compartments. Although pannexin-1 (PANX1) channels have been proposed to be critical in this process, CALHM1 (calcium homeostasis modulator) channels have emerged as the primary mediators of tastant-stimulated ATP release. Functional CALHM1 channels are hexameric complexes that are gated by depolarization and are highly permeable to Ca2+, as well as to ATP. These permeability characteristics present two challenges for the optimal function of this synapse: how to generate adequate local [ATP] within the presynaptic microcompartment of open-gated CALHM1 channels to sustain ATP efflux during taste sensing, while also counteracting Ca2+ influx to minimize global increases in cytosolic Ca2+ concentrations within type II cells. Type II cells solve this dilemma by juxtaposing atypically large mitochondria, with expanded cristae and ATP stores, within 30 nm of the clustered CALHM1 channels. These large mitochondria provide a ready reserve of ATP for robust efflux into the synaptic cleft during brief action potential trains while also presenting a physical barrier that localizes increased Ca2+ concentrations to the subsynaptic compartment. The broader expression of CALHM1 channels and P2X receptors within the central nervous system suggests roles for these atypical synapses in additional intercellular signaling pathways.

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