{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:18:15Z","timestamp":1791281895447,"version":"4.1.0"},"reference-count":67,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,3,3]],"date-time":"2006-03-03T00:00:00Z","timestamp":1141344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2006,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Elevation of the intracellular calcium concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) to levels below 1\u2003\u00b5<jats:sc>m<\/jats:sc> alters synaptic transmission and induces short\u2010term plasticity. To identify calcium sensors involved in this signalling, we investigated soluble C2 domain\u2010containing proteins and found that both DOC2A and DOC2B are modulated by submicromolar calcium levels. Fluorescent\u2010tagged DOC2A and DOC2B translocated to plasma membranes after [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> elevation. DOC2B translocation preceded DOC2A translocation in cells co\u2010expressing both isoforms. Half\u2010maximal translocation occurred at 450 and 175\u2003n<jats:sc>m<\/jats:sc>[Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> for DOC2A and DOC2B, respectively. This large difference in calcium sensitivity was accompanied by a modest kinetic difference (halftimes, respectively, 2.6 and 2.0\u2003s). The calcium sensitivity of DOC2 isoforms can be explained by predicted topologies of their C2A domains. Consistently, neutralization of aspartates D218 and D220 in DOC2B changed its calcium affinity. In neurones, both DOC2 isoforms were reversibly recruited to the plasma membrane during trains of action potentials. Consistent with its higher calcium sensitivity, DOC2B translocated at lower depolarization frequencies. Styryl dye uptake experiments in hippocampal neurones suggest that the overexpression of mutated DOC2B alters the synaptic activity. We conclude that both DOC2A and DOC2B are regulated by neuronal activity, and hypothesize that their calcium\u2010dependent translocation may regulate synaptic activity.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2006.03755.x","type":"journal-article","created":{"date-parts":[[2006,3,3]],"date-time":"2006-03-03T11:00:57Z","timestamp":1141383657000},"page":"818-833","source":"Crossref","is-referenced-by-count":89,"title":["DOC2A and DOC2B are sensors for neuronal activity with unique calcium\u2010dependent and kinetic properties"],"prefix":"10.1111","volume":"97","author":[{"given":"Alexander J. 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