Supplementary Table 1. Synaptic proteins discussed in this review
Family/subfamily Features
Name Protein properties Mouse mutant phenotype
Other names Expression in adult rodents
Mouse genome annotation
rab3 subfamily 4 members (A-D) in mammals
small GTPases
(for reviews, see Takai et al. 1996; Fukuda 2008)
Quadruple -/- die shortly after birth
respiratory failure
synapse structure appears normal
30% decrease in evoked transmitter release (chn)
decreased vesicular release probability
(Schlüter et al. 2004)
rab3a Small GTP-binding protein -/- viable and fertile
Chromosome 8, NC_000074.5 localized to synaptic vesicles most synaptic parameters normal
(73278578..73282585) (Fischer von Mollard et al. 1990) depression after repetitive stimuli increased (hs)
dissociates from vesicular membrane (Geppert et al. 1994b, 1997)
after exocytosis
(Fischer von Mollard et al. 1991)
Synaptosome-associated protein/ Neuronally expressed SNAP 25
SNAP family ubiquitously expressed SNAP 23
(for a review, see Hodel 1998)
Snap25 SNARE complex formation -/- not obtained live
Chromosome 2, NC_000068.6 with syntaxin and synaptobrevin/VAMP at E18.5 in expected Mendelian ratio
(136539186..136608164) (Söllner et al. 1993) no evoked endplate potentials (NMJ)
no KCl-induced endocytosis (chn)
(Washbourne et al. 2002)
Synapsin family Neuron-specific phosphoproteins abundant on synaptic vesicles
interact with lipid and protein components of synaptic vesicles
interact with various cytoskeletal proteins including actin
different isoforms generated by alternative splicing
3 genes in mammals
(for reviews, see Südhof et al. 1989; Hilfiker et al. 1999; Cesca et al. 2010)
Synapsin I, Syn1 6% of synaptic vesicle protein -/- viable and fertile
Chromosome X, NC_000086.6 (Huttner et al. 1983) no changes in synaptic architecture of the brain
(20437637..20498044, compl.) increase in paired-pulse facilitation (hs)
no major alteration in other synaptic parameters
(Rosahl et al. 1993)
vesicle exocytosis and recycling vesicle pool decreased (chn)
(Ryan et al. 1996)
Synaptic vesicle protein 2/SV2 family Integral membrane protein of secretory vesicles
(Lowe et al. 1988)
3 highly homologous members with different expression patterns
(Bajjalieh et al. 1994; Janz and Südhof 1999)
12 potential transmembrane regions not reflected in intron placements
(Janz et al. 1999a)
synaptotagmin binding (Schivell et al. 2005)
Double -/- die postnatally
severe seizures
sustained increases in Ca2+-dependent synaptic transmission
when stimulated repeatedly (chn)
(Janz et al. 1999a)
Sv2a Widely expressed in neurons -/- die postnatally
Chromosome 3, NC_000069.5 (Bajjalieh et al. 1994) severe seizures
(95985150..95999106) no abnormalities (chn)
(Janz et al. 1999a)
Sv2b More restricted neuronal expression -/- viable and fertile
Chromosome 7, NC_000073.5 (Bajjalieh et al. 1994) no abnormalities (chn)
(82259780..82454148, compl.) (Janz et al. 1999a)
elevated resting and evoked Ca2+ signals
changes in synaptic vesicle dynamics and synaptic strength (rbn)
(Wan et al. 2010)
Synaptobrevin/VAMP family Two highly homologous members
integral membrane proteins in synaptic vesicles
(Trimple et al. 1988; Baumert et al. 1989)
distinct but partially overlapping expression
(Elferink et al. 1989)
SNARE complex formation with syntaxin and Snap-25
(Söllner et al. 1993; Sutton et al. 1998)
synaptophysin binding alternative to syntaxin binding
(Edelmann et al. 1995)
Synaptobrevin 1/VAMP 1 Predominant in spinal cord -/- die around P15
Chromosome 6, NC_000072.5 (Elferink et al. 1989; noticeably immobile by P10
(125165599..125172324) Liu et al. 2011) (Nystuen et al. 2007)
function but not structure of NMJ altered
spontaneous and evoked synaptic activity reduced
pronounced asynchrony in neurotransmitter release
paired-pulse facilitation enhanced
reduced sensitivity and cooperativity to Ca2+
(Liu et al. 2011)
Synaptobrevin 2/VAMP 2 Most abundant isoform in brain -/- die immediately after birth
Chromosome 11, NC_000077.5 (Elferink et al. 1989; Trimble et al. 1990; normal brain anatomy
(68902030..68905883) Raptis et al. 2005; Liu et al. 2011) evoked and spontaneous synaptic vesicle exocytosis
severely but not completely decreased (chn)
deficient Ca2+-stimulation of synaptic fusion
(Schoch et al. 2001)
fast synaptic vesicle endocytosis compromised
(Deák et al. 2004)
Synaptophysin subfamily Two members within the synaptophysin/connexin family
integral membrane protein with four putative transmembrane domains
(Jahn et al. 1985; Südhof et al. 1987; Knaus et al. 1990)
Synaptophysin/Syp Major synaptic vesicle protein -/- viable and fertile
synaptophysin 1/p38 (Jahn et al. 1985) (Eshkind and Leube 1995)
Chromosome X, NC_000086.6 in all major brain areas normal brain structure
(7215706..7230382) (Marquèze-Pouey et al. 1991; (Janz et al. 1999b)
Fykse et al. 1993) normal synaptic transmission (hs)
no changes in synaptic plasticity
(McMahon et al. 1996)
learning impairment
(Schmitt et al. 2009)
compromised synaptobrevin II retrieval during endocytosis
(Gordon et al. 2011)
Synaptoporin/Synpr Copurifies with synaptic vesicles
Synaptophysin 2 (Knaus et al. 1990)
Chromosome 14, NC_000080.5 restricted to selected neuron populations
(14117294..14447983) (Marquèze-Pouey et al. 1991;
Fykse et al. 1993)
Synaptotagmin family 16 mammalian family members
integral membrane proteins mostly localized to synaptic and secretory vesicles
(for a review, see Pang and Südhof 2010)
many, not all with Ca2+-dependent phospholipid and syntaxin binding
(Brose et al. 1992; Li et al. 1995)
Synaptotagmin I/Syt1 Partial overlap with Syt2 expression -/- die within 2d after birth
Chromosome 10, NC_000076.5 predominant in rostral brain regions normal brain architecture
(107935305..108447675, compl.) postganglionic sympathetic neurons neurotransmission impaired (chn)
(Ullrich et al. 1994) no changes in Syt2 levels
Syntaxin, Synaptobrevin and Snap25 detected
Ca2+ binding fast component of Ca2+-dependent transmission blocked
(Geppert et al. 1994a)
Synaptotagmin II/Syt2 Predominant in caudal brain regions -/- normal at birth
Chromosome 1, NC_000067.5 overlaps with Syt1 in cerebellum develop motor disfunction
(136543258..136645994) (Ullrich et al. 1994) perish at ~3 weeks
evoked release two-fold reduced in NMJ
Ca2+ binding expression of 14 synaptic proteins unaltered
(Pang et al. 2006)
Synaptotagmin IV/Syt4 No Ca2+ binding -/- viable, appear normal
Chromosome 18, NC_000084.5 impaired motor coordination
(31597462..31607069, compl.) ubiquitous throughout nervous system (Ferguson et al. 2000)
(Ullrich et al. 1994) altered plasticity and memory
(Ferguson et al. 2004)
Synaptotagmin VII/Syt7 Ca2+ binding -/- viable and fertile
Chromosome 19, NC_000085.5 no change in GABAergic transmission (ccn)
(10463580..10527671) highest expression in brain (Maximov et al. 2008)
low expression in non-neuronal tissue
(Li et al. 1995)
Syntaxin family Membrane-anchored proteins facing the cytoplasmic surface of cellular membranes
(Bennett et al. 1993)
15 genes in mammals (for a review, see Teng et al. 2001)
syntaxin 1A and 1B expressed neuronally, others ubiquitous
SNARE complex formation with synaptobrevin and Snap-25
(Söllner et al. 1993; Sutton et al. 1998)
Syntaxin 1A/Stx1a Interacts with synaptotagmin -/- viable and fertile
Chromosome 5, NC_000071.5 on plasma membrane at synaptic sites synaptic transmission normal (chn)
(135499442..135526969) (Bennett et al. 1992) impaired LTP (hs)
(Fujiwara et al. 2006)
Neurexin family Three members in mammals
neuronal plasmamembrane proteins
one transmembrane domain
extensive alternative splicing generates highly diverse extracellular domains
(for a review, see Missler and Südhof 1998)
Triple -/- die after birth
neurotransmitter release impaired (div)
synaptic Ca2+ channel function reduced
(Missler et al. 2003)
Neurexin I/Nrxn1 Alpha-latrotoxin binding -/- show slightly reduced postnatal survival
Chromosome 17, NC_000083.5 (Ushkaryov et al. 1992) (Missler et al. 2003)
(90432984..91492142, compl.)
Experimental system: chn cultured hippocampal neurons, hs hippocampal slices, NMJ neuromuscular junction, rbn isolated rod bipolar neurons, ccn cultured cortical neurons, div various brain slice and culture preparations
Mouse genome annotation data from http://www.ncbi.nlm.nih.gov/gene/ (November 2011).
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