POSSIBLE ROLE FOR CALMODULIN AND THE CA2+/CALMODULIN-DEPENDENT PROTEIN KINASE-II IN POSTSYNAPTIC NEUROTRANSMISSION

被引:29
作者
SIEKEVITZ, P
机构
[1] Rockefeller University, New York
关键词
D O I
10.1073/pnas.88.12.5374
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The theory presented here is based on results from in vitro experiments and deals with three proteins in the postsynaptic density/membrane - namely, calmodulin, the Ca2+/calmodulin-dependent protein kinase, and the voltage-dependent Ca2+ channel. It is visualized that, in vivo in the polarized state of the membrane, calmodulin is bound to the kinase; upon depolarization of the membrane and the intrusion of Ca2+, Ca2+-bound calmodulin activates the autophosphorylation of the kinase. Calmodulin is visualized as having less affinity for the phosphorylated form of the kinase and is translocated to the voltage-dependent Ca2+ channel. There, with its bound Ca2+, it acts as a Ca2+ sensor, to close off the Ca2+ channel of the depolarized membrane. At the same time, it is thought that the configuration of the kinase is altered by its phosphorylated states; by interacting with Na+ and K+ channels, it alters the electrical properties of the membrane to regain the polarized state. Calmodulin is moved to the unphosphorylated kinase to complete the cycle, allowing the voltage-dependent Ca2+ channel to be receptive to Ca2+ flux upon the next cycle of depolarization. Thus, the theory tries to explain (i) why calmodulin and the kinase reside at the postsynaptic density/membrane site, and (ii) what function autophosphorylation of the kinase may play.
引用
收藏
页码:5374 / 5378
页数:5
相关论文
共 79 条
[1]  
ANTHONY FA, 1988, J NEUROSCI, V8, P1245
[2]   IDENTIFICATION OF THE PROTEIN KINASE-C PHOSPHORYLATION SITE IN NEUROMODULIN [J].
APEL, ED ;
BYFORD, MF ;
AU, D ;
WALSH, KA ;
STORM, DR .
BIOCHEMISTRY, 1990, 29 (09) :2330-2335
[3]   INVIVO PHOSPHORYLATION OF POSTSYNAPTIC DENSITY PROTEINS [J].
BERMAN, RF ;
HULLIHAN, JP ;
KINNIER, WJ ;
WILSON, JE .
NEUROSCIENCE, 1984, 13 (03) :965-971
[4]   CALCIUM-TRANSPORT AND BUFFERING IN NEURONS [J].
BLAUSTEIN, MP .
TRENDS IN NEUROSCIENCES, 1988, 11 (10) :438-443
[5]   INTRACELLULAR CALCIUM HOMEOSTASIS [J].
CARAFOLI, E .
ANNUAL REVIEW OF BIOCHEMISTRY, 1987, 56 :395-433
[6]   CHARACTERIZATION OF NA+-INDEPENDENT GABA AND FLUNITRAZEPAM BINDING-SITES IN PREPARATIONS OF SYNAPTIC-MEMBRANES AND POSTSYNAPTIC DENSITIES ISOLATED FROM CANINE CEREBRAL-CORTEX AND CEREBELLUM [J].
CARLIN, RK ;
SIEKEVITZ, P .
JOURNAL OF NEUROCHEMISTRY, 1984, 43 (04) :1011-1017
[7]   FUNCTION OF CALMODULIN IN POSTSYNAPTIC DENSITIES .3. CALMODULIN-BINDING PROTEINS OF THE POSTSYNAPTIC DENSITY [J].
CARLIN, RK ;
GRAB, DJ ;
SIEKEVITZ, P .
JOURNAL OF CELL BIOLOGY, 1981, 89 (03) :449-455
[8]   ISOLATION AND CHARACTERIZATION OF POSTSYNAPTIC DENSITIES FROM VARIOUS BRAIN-REGIONS - ENRICHMENT OF DIFFERENT TYPES OF POSTSYNAPTIC DENSITIES [J].
CARLIN, RK ;
GRAB, DJ ;
COHEN, RS ;
SIEKEVITZ, P .
JOURNAL OF CELL BIOLOGY, 1980, 86 (03) :831-843
[9]  
CHEUNG WY, 1985, HARVEY LECT, V79, P173
[10]   CALCIUM CALMODULIN-DEPENDENT PROTEIN KINASE-II [J].
COLBRAN, RJ ;
SCHWORER, CM ;
HASHIMOTO, Y ;
FONG, YL ;
RICH, DP ;
SMITH, MK ;
SODERLING, TR .
BIOCHEMICAL JOURNAL, 1989, 258 (02) :313-325