Gene Symbol: Synj1
Description: synaptojanin 1
Alias: A930006D20Rik, AA675315, mKIAA0910, synaptojanin-1, synaptic inositol 1,4,5-trisphosphate 5-phosphatase 1
Species: mouse
Products:     Synj1

Top Publications

  1. Khvotchev M, Sudhof T. Developmentally regulated alternative splicing in a novel synaptojanin. J Biol Chem. 1998;273:2306-11 pubmed
    ..Biol. Chem. 272, 9625-9628). We now describe synaptojanin 2, a novel isoform of synaptojanin that, similar to synaptojanin 1, contains an N-terminal SAC1-like sequence and a central 5-phosphatase domain but a distinct, unique C-..
  2. MANI M, Lee S, Lucast L, Cremona O, Di Paolo G, De Camilli P, et al. The dual phosphatase activity of synaptojanin1 is required for both efficient synaptic vesicle endocytosis and reavailability at nerve terminals. Neuron. 2007;56:1004-18 pubmed
    ..the role of synaptojanin1 at nerve terminals, we performed quantitative synaptic vesicle recycling assays in synj1(-/-) neurons. Our studies show that synaptojanin1 is also required for normal vesicle endocytosis...
  3. Voronov S, Frere S, Giovedi S, Pollina E, Borel C, Zhang H, et al. Synaptojanin 1-linked phosphoinositide dyshomeostasis and cognitive deficits in mouse models of Down's syndrome. Proc Natl Acad Sci U S A. 2008;105:9415-20 pubmed publisher
    ..normal PtdIns(4,5)P(2) balance is required for proper neurotransmission, the phosphoinositide phosphatase synaptojanin 1 is a key regulator of its metabolism...
  4. Cremona O, Di Paolo G, Wenk M, Luthi A, Kim W, Takei K, et al. Essential role of phosphoinositide metabolism in synaptic vesicle recycling. Cell. 1999;99:179-88 pubmed
    ..A polyphosphoinositide phosphatase, synaptojanin 1, was identified as a major presynaptic protein associated with endocytic coated intermediates...
  5. Berman D, Dall Armi C, Voronov S, McIntire L, Zhang H, Moore A, et al. Oligomeric amyloid-beta peptide disrupts phosphatidylinositol-4,5-bisphosphate metabolism. Nat Neurosci. 2008;11:547-54 pubmed publisher
    ..This gene encodes synaptojanin 1, the main PtdIns(4,5)P2 phosphatase in the brain and at the synapses...
  6. Quesnel Vallieres M, Dargaei Z, Irimia M, Gonatopoulos Pournatzis T, Ip J, Wu M, et al. Misregulation of an Activity-Dependent Splicing Network as a Common Mechanism Underlying Autism Spectrum Disorders. Mol Cell. 2016;64:1023-1034 pubmed publisher
    ..Collectively, our results provide evidence that misregulation of an nSR100-dependent splicing network controlled by changes in neuronal activity is causally linked to a substantial fraction of autism cases. ..
  7. Milosevic I, Giovedi S, Lou X, Raimondi A, Collesi C, Shen H, et al. Recruitment of endophilin to clathrin-coated pit necks is required for efficient vesicle uncoating after fission. Neuron. 2011;72:587-601 pubmed publisher
  8. Herrera F, Chen Q, Fischer W, Maher P, Schubert D. Synaptojanin-1 plays a key role in astrogliogenesis: possible relevance for Down's syndrome. Cell Death Differ. 2009;16:910-20 pubmed publisher
    ..Our results strongly indicate that phosphatidylinositol metabolism plays a key role in astrogliogenesis. The relevance of our findings for Down's syndrome pathology is discussed. ..
  9. Di Paolo G, Sankaranarayanan S, Wenk M, Daniell L, Perucco E, Caldarone B, et al. Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice. Neuron. 2002;33:789-804 pubmed
    ..These defects correlate with increased mortality due to rare irreversible seizures and with major learning deficits, suggesting a critical role of amphiphysin for higher brain functions. ..

More Information


  1. Vázquez Carretero M, Carvajal A, Serrano Morales J, García Miranda P, Ilundáin A, Peral M. The Synaptojanins in the murine small and large intestine. J Bioenerg Biomembr. 2016;48:569-579 pubmed
    ..Herein we show that the small and large intestine express Synj1 and Synj2...
  2. Quadri M, Fang M, Picillo M, Olgiati S, Breedveld G, Graafland J, et al. Mutation in the SYNJ1 gene associated with autosomal recessive, early-onset Parkinsonism. Hum Mutat. 2013;34:1208-15 pubmed publisher
    ..SYNJ1 encodes synaptojanin 1, a phosphoinositide phosphatase protein with essential roles in the postendocytic recycling of synaptic ..
  3. Modregger J, Schmidt A, Ritter B, Huttner W, Plomann M. Characterization of Endophilin B1b, a brain-specific membrane-associated lysophosphatidic acid acyl transferase with properties distinct from endophilin A1. J Biol Chem. 2003;278:4160-7 pubmed
    ..However, in contrast to endophilins A, endophilin B1 does not bind to synaptojanin 1 and synapsin 1, and overexpression of its SH3 domain does not inhibit transferrin endocytosis...
  4. Gong L, De Camilli P. Regulation of postsynaptic AMPA responses by synaptojanin 1. Proc Natl Acad Sci U S A. 2008;105:17561-6 pubmed publisher
    ..We have genetically tested the hypothesis that synaptojanin 1, a phosphoinositide phosphatase implicated in the endocytosis of synaptic vesicles presynaptically, may also ..
  5. Volpicelli Daley L, Lucast L, Gong L, Liu L, Sasaki J, Sasaki T, et al. Phosphatidylinositol-4-phosphate 5-kinases and phosphatidylinositol 4,5-bisphosphate synthesis in the brain. J Biol Chem. 2010;285:28708-14 pubmed publisher
  6. Soda K, Balkin D, Ferguson S, Paradise S, Milosevic I, Giovedi S, et al. Role of dynamin, synaptojanin, and endophilin in podocyte foot processes. J Clin Invest. 2012;122:4401-11 pubmed publisher
    ..In addition, we demonstrated that while synaptojanin 1 (Synj1) KO mice and endophilin 1 (Sh3gl2), endophilin 2 (Sh3gl1), and endophilin 3 (Sh3gl3) triple-KO mice had ..
  7. McIntire L, Berman D, Myaeng J, Staniszewski A, Arancio O, Di Paolo G, et al. Reduction of synaptojanin 1 ameliorates synaptic and behavioral impairments in a mouse model of Alzheimer's disease. J Neurosci. 2012;32:15271-6 pubmed publisher
    ..Haploinsufficiency of the gene encoding synaptojanin 1 (Synj1), a major PI(4,5)P(2) phosphatase in the brain, provided protection against PI(4,5)P(2) breakdown and ..
  8. Cossec J, Lavaur J, Berman D, Rivals I, Hoischen A, Stora S, et al. Trisomy for synaptojanin1 in Down syndrome is functionally linked to the enlargement of early endosomes. Hum Mol Genet. 2012;21:3156-72 pubmed publisher
    ..This locus contains the gene encoding the phosphoinositide phosphatase synaptojanin 1 (SYNJ1), a key regulator of the signalling phospholipid phosphatidylinositol-4,5-biphosphate that has been ..
  9. Liu C, Morishima M, Yu T, Matsui S, Zhang L, Fu D, et al. Genetic analysis of Down syndrome-associated heart defects in mice. Hum Genet. 2011;130:623-32 pubmed publisher
    ..Therefore, we established the smallest critical genomic region for DS-associated heart defects to lay the foundation for identifying the causative gene(s) for this phenotype. ..
  10. Cremona O, Nimmakayalu M, Haffner C, Bray Ward P, Ward D, De Camilli P. Assignment of SYNJ1 to human chromosome 21q22.2 and Synj12 to the murine homologous region on chromosome 16C3-4 by in situ hybridization. Cytogenet Cell Genet. 2000;88:89-90 pubmed
  11. Strochlic T, Concilio S, Viaud J, Eberwine R, Wong L, Minden A, et al. Identification of neuronal substrates implicates Pak5 in synaptic vesicle trafficking. Proc Natl Acad Sci U S A. 2012;109:4116-21 pubmed publisher
    ..These results implicate Pak5 in Pacsin1- and Synaptojanin1-mediated synaptic vesicle trafficking and may partially account for the cognitive and behavioral deficits observed in group II Pak-deficient mice. ..
  12. Cao M, Wu Y, Ashrafi G, McCartney A, Wheeler H, Bushong E, et al. Parkinson Sac Domain Mutation in Synaptojanin 1 Impairs Clathrin Uncoating at Synapses and Triggers Dystrophic Changes in Dopaminergic Axons. Neuron. 2017;93:882-896.e5 pubmed publisher
    b>Synaptojanin 1 (SJ1) is a major presynaptic phosphatase that couples synaptic vesicle endocytosis to the dephosphorylation of PI(4,5)P2, a reaction needed for the shedding of endocytic factors from their membranes...
  13. Kim W, Chang S, Daniell L, Cremona O, Di Paolo G, De Camilli P. Delayed reentry of recycling vesicles into the fusion-competent synaptic vesicle pool in synaptojanin 1 knockout mice. Proc Natl Acad Sci U S A. 2002;99:17143-8 pubmed
    b>Synaptojanin 1 is a polyphosphoinositide phosphatase implicated in synaptic vesicle recycling...
  14. Zhu L, Zhong M, Zhao J, Rhee H, Caesar I, Knight E, et al. Reduction of synaptojanin 1 accelerates A? clearance and attenuates cognitive deterioration in an Alzheimer mouse model. J Biol Chem. 2013;288:32050-63 pubmed publisher
    Recent studies link synaptojanin 1 (synj1), the main phosphoinositol (4,5)-biphosphate phosphatase (PI(4,5)P2-degrading enzyme) in the brain and synapses, to Alzheimer disease...
  15. Zhu L, Zhong M, Elder G, Sano M, Holtzman D, Gandy S, et al. Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer's disease pathogenesis. Proc Natl Acad Sci U S A. 2015;112:11965-70 pubmed publisher
    ..changes are secondary to increased expression of a PIP2-degrading enzyme, the phosphoinositol phosphatase synaptojanin 1 (synj1), in ApoE4 carriers...
  16. Kurakin A, Wu S, Bredesen D. Atypical recognition consensus of CIN85/SETA/Ruk SH3 domains revealed by target-assisted iterative screening. J Biol Chem. 2003;278:34102-9 pubmed
    ..b>Synaptojanin 1, PAK2, ZO-2, and TAFII70, which contain CIN85 SH3 recognition consensus sites, were selectively precipitated ..
  17. Pan P, Li X, Wang J, Powell J, Wang Q, Zhang Y, et al. Parkinson's Disease-Associated LRRK2 Hyperactive Kinase Mutant Disrupts Synaptic Vesicle Trafficking in Ventral Midbrain Neurons. J Neurosci. 2017;37:11366-11376 pubmed publisher
    ..Additionally, we found MB-specific impairment of SV endocytosis in neurons carrying heterozygous deletion of SYNJ1 (PARK20), a gene that is associated with recessive Parkinsonism...
  18. Chang Ileto B, Frere S, Chan R, Voronov S, Roux A, Di Paolo G. Synaptojanin 1-mediated PI(4,5)P2 hydrolysis is modulated by membrane curvature and facilitates membrane fission. Dev Cell. 2011;20:206-18 pubmed publisher
    ..assays with liposomes of varying diameters, we show that the major synaptic phosphoinositide phosphatase, synaptojanin 1 (Synj1), acts with membrane curvature generators/sensors, such as the BAR protein endophilin, to ..
  19. Trempe J, Chen C, Grenier K, Camacho E, Kozlov G, McPherson P, et al. SH3 domains from a subset of BAR proteins define a Ubl-binding domain and implicate parkin in synaptic ubiquitination. Mol Cell. 2009;36:1034-47 pubmed publisher
    ..The findings identify a pathway for the recruitment of synaptic substrates to parkin with the potential to explain the defects in synaptic transmission observed in recessive forms of PD. ..