Absence of synapsin I and II is accompanied by decreases in vesicular transport of specific neurotransmitters

被引:71
作者
Bogen, IL
Boulland, JL
Mariussen, E
Wright, MS
Fonnum, F
Kao, HT
Walaas, SI
机构
[1] Univ Oslo, Dept Biochem, Inst Basic Med Sci, N-0317 Oslo, Norway
[2] Univ Oslo, Mol Neurobiol Res Grp, Fac Med, N-0317 Oslo, Norway
[3] Univ Oslo, Ctr Biotechnol, N-0317 Oslo, Norway
[4] Norwegian Inst Air Res, Kjeller, Norway
[5] Univ Hosp Oslo, Rikshosp, Dept Pediat Res, Oslo, Norway
[6] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA
关键词
colocalization; knockout; neurotransmitter transport; synapsin; synaptic vesicles; vesicular transporters;
D O I
10.1111/j.1471-4159.2005.03636.x
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
Studies of synapsin-deficient mice have shown decreases in the number of synaptic vesicles but knowledge about the consequences of this decrease, and which classes of vesicles are being affected, has been lacking. In this study, glutamatergic, GABAergic and dopaminergic transport has been analysed in animals where the genes encoding synapsin I and II were inactivated. The levels of the vesicular glutamate transporter (VGLUT) 1, VGLUT2 and the vesicular GABA transporter (VGAT) were decreased by approximately 40% in adult forebrain from mice devoid of synapsin I and II, while vesicular monoamine transporter (VMAT) 2 and VGLUT3 were present in unchanged amounts compared with wild-type mice. Functional studies on synaptic vesicles showed that the vesicular uptake of glutamate and GABA was decreased by 41 and 23%, respectively, while uptake of dopamine was unaffected by the lack of synapsin I and II. Double-labelling studies showed that VGLUT1 and VGLUT2 colocalized fully with synapsin I and/or II in the hippocampus and neostriatum, respectively. VGAT showed partial colocalization, while VGLUT3 and VMAT2 did not colocalize with either synapsin I or II in the brain areas studied. In conclusion, distinct vesicular transporters show a variable degree of colocalization with synapsin proteins and, hence, distinct sensitivities to inactivation of the genes encoding synapsin I and II.
引用
收藏
页码:1458 / 1466
页数:9
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