Disease relevance of SYNJ1

• Selection of ligands by panning of domain libraries displayed on phage lambda reveals new potential partners of synaptojanin 1 [1].
• Excessive expression of synaptojanin in brains with Down syndrome [2].

Psychiatry related information on SYNJ1

• Analysis of SYNJ1, a candidate gene for 21q22 linked bipolar disorder: a replication study [3].

High impact information on SYNJ1

• These findings provide a mechanistic basis for localized inositide generation at sites of clathrin-coated bud formation, which, with recruitment of inositide binding proteins and subsequent synaptojanin-mediated phosphoinositide hydrolysis, may regulate coated vesicle formation and uncoating [4].
• EphrinB-EphB signalling regulates clathrin-mediated endocytosis through tyrosine phosphorylation of synaptojanin 1 [5].
• In this issue of Neuron, Schuske et al. and Verstreken et al. show that the lipid-modifying enzyme endophilin recruits and stabilizes the polyphosphoinositide phosphatase synaptojanin at nerve terminals [6].
• Here, we show that compounds that disrupt interactions of the SH3 domain of endophilin with dynamin and synaptojanin impair synaptic vesicle endocytosis in a living synapse [7].
• Free clathrin-coated vesicles were induced by a peptide-blocking endophilin's SH3 domain and by antibodies to the proline-rich domain (PRD) of synaptojanin [7].

Biological context of SYNJ1

• Assignment of SYNJ1 to human chromosome 21q22.2 and Synj12 to the murine homologous region on chromosome 16C3-4 by in situ hybridization [8].
• In vitro competitive binding assays demonstrate that EEN displays stronger binding affinity than Abi-1 and may compete with it for synaptojanin [9].
• Biotinylated SH3 domains were also used for specific identification of target proline-rich sequences in synaptojanin and ACK1 on synthetic peptides arrays [10].
• In order to investigate SNX9 further we have made use of a novel in vivo biotinylation system to label various GST-SH3 domains and perform blot overlays, thereby identifying synaptojanin-1 as a partner for SNX9 [10].
• They interact with dynamin and synaptojanin via their COOH-terminal SH3 domain, whereas their central regions contain binding sites for clathrin and for the clathrin adaptor AP-2 [11].

Anatomical context of SYNJ1

• Expression studies show that synaptojanin is strongly expressed in bone marrow and immature leukaemic cell lines, very weakly in peripheral blood leukocytes and absent in Raji, a mature B cell line [9].
• The dramatic effects of the SH3 domain of endophilin led us to propose a model for the temporal order of addition of endophilin and its binding partner synaptojanin in the coated vesicle cycle [12].
• It has been demonstrated that the amphiphysins also bind to clathrin, and we have proposed that this interaction may help to target synaptojanin and dynamin to sites of synaptic vesicle endocytosis [13].
• Antibodies raised against the synaptojanin 2B-specific carboxyl-terminal region identified a 160-kDa protein in brain and testis [14].
• These results suggest that synaptojanin 2B has a partially overlapping function with synaptojanin 1 in nerve terminals, with additional roles in neurons and other cells including spermatids [14].

Associations of SYNJ1 with chemical compounds

• Synaptojanin 1 is an inositol 5-phosphatase with a putative role in clathrin-mediated endocytosis [15].
• These include the GTPase dynamin, the lysophosphatidic acid acyl transferase endophilin, and the phosphoinositide phosphatase synaptojanin [16].
• Peptides that mimic binding sites in the potential EH(3) targets Rab, synaptojanin, and the cation-dependent mannose 6-phosphate receptor were used to explore wild-type and mutant affinities [17].
• Simultaneous progressive changes in distribution of amphiphysin, synaptojanin, and subunits of NMDA- and AMPA-receptors provide a strong indication of dysfunctional synaptic trafficking [18].
• EphB2 causes tyrosine phosphorylation in the proline-rich domain of synaptojanin 1, and inhibits both the interaction with endophilin and the 5'-phosphatase activity of synaptojanin 1 [5].

Other interactions of SYNJ1

• SNX9 as an adaptor for linking synaptojanin-1 to the Cdc42 effector ACK1 [10].
• We have precisely mapped the target peptides on human synaptojanin that are recognized by the SH3 domains of endophilins and amphiphysin and proven that they are distinct [19].
• Through its SH3 domain, endophilin bound to proline-rich domains (PRDs) in other endocytic proteins, including synaptojanin and dynamin [20].
• This pathway is synaptojanin independent and requires the GTPase dynamin [21].
• Furthermore, we report that synaptojanin-170, an alternatively spliced isoform of synaptojanin 1, binds Eps15, a clathrin coat-associated protein [15].

Analytical, diagnostic and therapeutic context of SYNJ1

• Immunofluorescence showed that synaptojanin 2B is localized at nerve terminals in brain and at the spermatid manchette in testis [14].
• Western blotting with synaptojanin confirmed the increased expression in DS brains [2].
• Immunohistochemistry consistently revealed the localization of synaptojanin in Cajal--Retzius cells, cortical plate neurons, subplate neurons, intermediate neurons, germinal matrix cells and the ventricular neuroepithelium of the fetal cerebrum [22].
• Correcting the sequence alignment to match the residues at the ends of two of the molegos that are absolutely conserved in each of the three families greatly improved the local structural alignment of APEs, DNase-1 and synaptojanin [23].

References