High impact information on Synj1

• Mutations in synaptojanin disrupt synaptic vesicle recycling [1].
• This effect of InsP(6) depends on calcineurin-induced dephosphorylation and is accounted for by both activation of protein kinase C and inhibition of the phosphoinositide phosphatase synaptojanin and thereby formation of phosphatidylinositol 4,5-bisphosphate [2].
• Synaptojanin 2 is a ubiquitously expressed polyphosphoinositide phosphatase that displays a high degree of homology in its catalytic domains with synaptojanin 1 [1,2] [3].
• Neurons of synaptojanin 1-deficient mice display an increase in clathrin-coated vesicles and delayed reentry of recycling vesicles into the fusion-competent vesicle pool, but no defects in early steps of endocytosis [3,4] [3].
• Developmentally regulated alternative splicing in a novel synaptojanin [4].

Biological context of Synj1

• Transfection studies demonstrated that synaptojanin 2, like synaptojanin 1, is an active PIP phosphatase [4].
• Although it exhibits no homology to synaptojanin 1 in this region, synaptojanin 2 also contains an open reading frame in the 3' region that is subject to alternative splicing [4].
• This inhibitory phenotype is rescued by overexpression of wild-type synaptojanin 2, but not of wild-type synaptojanin 1 or mutant synaptojanin 2 that is deficient in 5'-phosphatase activity [3].

Anatomical context of Synj1

• Synaptojanin 1 is a polyphosphoinositide phosphatase implicated in synaptic vesicle recycling [5].

Analytical, diagnostic and therapeutic context of Synj1

• We used FM1-43 imaging and electron microscopy in cultured cortical neurons from control and synaptojanin 1 knockout mice to study how the absence of this protein affects specific steps of the synaptic vesicle cycle [5].

References