Absence of synapsin I and II is accompanied by decreases in vesicular transport of specific neurotransmitters.
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.
Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. i.l.bogen@medisin.uio.no
Inger Lise
IL
Bogen
Jean-Luc
JL
Boulland
Espen
E
Mariussen
Marianne S
MS
Wright
Frode
F
Fonnum
Hung-Teh
HT
Kao
S Ivar
SI
Walaas
D000818:Animals; D005455:Fluorescent Antibody Technique / Q000379:methods; D015870:Gene Expression / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal / Q000379:methods; D018377:Neurotransmitter Agents / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013347:Subcellular Fractions / Q000378:metabolism; D016704:Synapsins / Q000172:deficiency / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism; D050481:Vesicular Neurotransmitter Transport Proteins / Q000145:classification / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D016704:Synapsins; D050481:Vesicular Neurotransmitter Transport Proteins