title: Role of annexin A6 isoforms in catecholamine secretion by PC12 cells: distinct influence on calcium response.
abstract: Noradrenaline and adrenaline are secreted by adrenal medulla chromaffin cells via exocytosis. Exocytosis of catecholamines occurs after cell stimulation with various endogenous activators such as nicotine or after depolarization of the plasma membrane and is regulated by calcium ions. Cytosolic [Ca(2+)] increases in response to cell excitation and triggers a signal-initiated secretion. Annexins are known to participate in the regulation of membrane dynamics and are also considered to be involved in vesicular trafficking. Some experimental evidence suggests that annexins may participate in Ca(2+)-regulated catecholamine secretion. In this report the effect of annexin A6 (AnxA6) isoforms 1 and 2 on catecholamine secretion has been described. Overexpression of AnxA6 isoforms and AnxA6 knock-down in PC12 cells were accompanied by almost complete inhibition or a 20% enhancement of dopamine secretion, respectively. AnxA6-1 and AnxA6-2 overexpression reduced Delta[Ca(2+)](c) upon depolarization by 32% and 58%, respectively, while AnxA6 knock-down increased Delta[Ca(2+)](c) by 44%. The mechanism of AnxA6 action on Ca(2+) signalling is not well understood. Experimental evidence suggests that two AnxA6 isoforms interact with different targets engaged in regulation of calcium homeostasis in PC12 cells.
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, PL-02-093 Warsaw, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Podszywalow-Bartnicka
authors.forename: Michalina
authors.initials: M
authors.lastname: Kosiorek
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Piwocka
authors.forename: Ewa
authors.initials: E
authors.lastname: Sikora
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Zablocki
authors.forename: Slawomir
authors.initials: S
authors.lastname: Pikula
mesh_terms: D000818:Animals; D017317:Annexin A6 / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D016716:PC12 Cells; D020033:Protein Isoforms / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017317:Annexin A6; D002395:Catecholamines; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D002118:Calcium; D004298:Dopamine