Calmodulin directly gates gap junction channels

被引:93
作者
Peracchia, C [1 ]
Sotkis, A [1 ]
Wang, XG [1 ]
Peracchia, LL [1 ]
Persechini, A [1 ]
机构
[1] Univ Rochester, Sch Med & Dent, Dept Pharmacol & Physiol, Rochester, NY 14642 USA
关键词
D O I
10.1074/jbc.M004007200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cytosolic changes control gap junction channel gating via poorly understood mechanisms. In the past two decades calmodulin participation in gating has been suggested, but compelling evidence for it has been lacking. Here we show that calnodulin indeed is associated with gap junctions and plays a direct role in chemical gating. Expression of a calmodulin mutant with the N-terminal EF hand pair replaced by a copy of the C-terminal pair dramatically increases the chemical gating sensitivity of gap junction channels composed of connexin 32 and decreases their sensitivity to transjunctional voltage. The increased chemical gating sensitivity, most likely because of the higher overall Ca2+ binding affinity of this mutant as compared with native calnodulin, and the decreased voltage sensitivity are only observed when the mutant is expressed before connexin 32, This indicates that the mutant, and by extension native calmodulin, must interact with connexin 32 before gap junctions are formed. Immunofluorescence data suggest further that this interaction leads to incorporation of native or mutant calmodulin into the connexon as an integral regulatory subunit.
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收藏
页码:26220 / 26224
页数:5
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