Synaptojanin Is Recruited by Endophilin to Promote Synaptic Vesicle Uncoating

Verstreken, Patrik; Koh, Tong-Wey; Schulze, Karen L.; Zhai, R. Grace; Hiesinger, P. Robin; Zhou, Yi; Mehta, Sunil; Cao, Yu; Roos, Jack; Bellen, Hugo J.

doi:10.1016/s0896-6273(03)00644-5

Cited by 371 publications

(481 citation statements)

References 43 publications

Supporting

Mentioning

446

Contrasting

Unclassified

Order By: Relevance

“…Other structures that could recruit endophilin include caveolae (34) or micropinocytic vesicles. Although dynamin was recruited to CCPs independent of endophilin expression, the accumulation of SJ1-145 to CCPs strongly depended on the expression of endophilin, consistent with an important role of endophilin in the targeting of SJ1 (20,21,23 tial association by its BAR domain, with the curved membrane of the vesicle stalk (5,18,25,26); (ii) interaction by its SH3 domain with dynamin (15); and (iii) binding, again by its SH3 domain, with cargo proteins present in the nascent vesicle (35)(36)(37). Because endophilin exists as a dimer (38), it may simultaneously bind two different proteins, e.g., synaptojanin and either vesicle cargo or dynamin, by the two SH3 domains of the dimer.…”

Section: Discussionsupporting

confidence: 52%

“…Endophilin is thought to be a particularly important interactor of SJ1 and to play a major role in its recruitment to sites of endocytosis (2,15,19,20). In both flies and worms, mutations of endophilin and synaptojanin have similar phenotypes, and loss of endophilin results in destabilization and mislocalization of synaptojanin (21)(22)(23)(24). Endophilin, which binds synaptojanin by its C-terminal SH3 domain, also contains an N-terminal BAR domain.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Two synaptojanin 1 isoforms are recruited to clathrin-coated pits at different stages

Perera¹,

Zoncu

Lucast

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

153

186

View full text Add to dashboard Cite

Phosphoinositides are thought to play an important role in clathrincoated pit (CCP) dynamics. Biochemical and structural studies have shown a direct interaction of phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P 2] with endocytic clathrin adaptors, whereas functional studies using cell-free systems or intact cells have demonstrated the importance of PI(4,5)P 2 synthesis and dephosphorylation in clathrin coating and uncoating, respectively. Furthermore, genetic manipulations of kinases and phosphatases involved in PI(4,5)P 2 metabolism result in major defects in synaptic vesicle recycling and other forms of clathrin-dependent endocytosis. However, live imaging studies of these enzymes at CCPs have not been conducted. We have used multicolor total internal reflection fluorescence microscopy (TIRFM) to visualize the spatialtemporal recruitment of synaptojanin 1 (SJ1), a polyphosphoinositide phosphatase, and its binding partner endophilin to CCPs. Strikingly, we observed differential temporal recruitment of the two major SJ1 splice variants to CCPs. The 145-kDa isoform, the predominant isoform expressed in the brain, was rapidly recruited as a ''burst,'' together with endophilin, at a late stage of CCP formation. In contrast, the nonneuronal ubiquitously expressed 170-kDa isoform of SJ1 was present at all stages of CCP formation. These results raise the possibility that dynamic phosphoinositide metabolism may occur throughout the lifetime of a CCP.dynamin ͉ endocytosis ͉ endophilin ͉ phosphoinositides ͉ phosphatidylinositol (4,5)-bisphosphate

show abstract

Section: Discussionsupporting

confidence: 52%

mentioning

confidence: 99%

Two synaptojanin 1 isoforms are recruited to clathrin-coated pits at different stages

Perera¹,

Zoncu

Lucast

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

153

186

View full text Add to dashboard Cite

show abstract

“…Simplistically, defective synaptic release might be entirely a secondary effect of a primary impairment in vesicle pool maintenance, due to disrupted vesicle endocytosis. However, recent studies of endophilin and synaptojanin endocytic mutants suggest that only a surprisingly small number of synaptic vesicles is actually required to support normal synaptic function at basal stimulation frequencies: In both endophilin and synaptojanin mutants, basal synaptic transmission is completely normal despite the near elimination of the presynaptic vesicle population, and the loss of synaptic uptake of FM1-43 (Verstreken et al, 2002(Verstreken et al, , 2003Dickman et al, 2005). This raises the question that STNB may be involved in other processes that affect exocytosis, apart from limiting the availability of vesicles.…”

Section: Discussionmentioning

confidence: 99%

“…Similar paradigms have recently been used to unveil functional deficits in endophilin and synaptojanin mutants (Verstreken et al, 2002(Verstreken et al, , 2003Dickman et al, 2005). The applied stimulation paradigm consisted of a 1 minute baseline interval with stimulation at 0.1Hz, a 10 minute interval with high-frequency stimulation (HFS) at 10Hz to strongly challenge synapses, and a subsequent recovery interval with 0.1Hz stimulation (Fig.…”

Section: Synaptic Depression Is Altered In Severe Stnb Hypomorphic Mumentioning

confidence: 99%

Stoned B mediates sorting of integral synaptic vesicle proteins

Mohrmann¹,

Matthies²,

Woodruff³

et al. 2008

Neuroscience

View full text Add to dashboard Cite

A continuous supply of fusion-competent synaptic vesicles is essential for sustainable neurotransmission. Drosophila mutations of the dicistronic stoned locus disrupt normal vesicle cycling and cause functional deficits in synaptic transmission. Although both Stoned A and B proteins putatively participate in reconstituting synaptic vesicles, their precise function is still unclear. Here we investigate the effects of progressive depletion of Stoned B (STNB) on the release properties of neuromuscular synapses using a novel set of synthetic STNB hypomorphic alleles. Decreasing neuronal STNB expression to ≤35% of wildtype level causes a strong reduction in EJC amplitude at low stimulation frequencies and a marked slowing in synaptic depression during high-frequency stimulation, suggesting vesicle depletion is attenuated by decreased release probability. Recovery from synaptic depression after prolonged stimulation is also decelerated in mutants, indicating a delayed recovery of fusion-ready vesicles. These phenotypes appear not to be due to a diminished vesicle population, since the docked vesicle pool is ultrastructurally unaffected, and the total number of vesicles is only slightly reduced in these hypomorphs, unlike lethal stoned mutants. Therefore, we conclude that STNB not only functions as an essential component of the endocytic complex for vesicle reconstitution, as previously proposed, but also regulates the competence of recycled vesicles to undergo fusion. In support of such role of STNB, synaptic levels of the vesicular glutamate transporter (vGLUT) and synaptotagmin-1 are strongly reduced with diminishing STNB function, while other synaptic proteins are largely unaffected. We conclude that STNB organizes the endocytic sorting of a subset of integral synaptic vesicle proteins thereby regulating the fusion-competence of the recycled vesicle.

show abstract

“…The Nterminus mainly participates at the base of the membrane invagination in clathrin-coated endocytosis [14][15][16] . In brain, the SH3 domain interacts selectively with proteins containing a proline-rich domain (PRD), such as synaptojanin, amphiphysin and GTPase dynamin [17][18][19][20][21][22] . Our previous studies found an atypical PRD embedded within endophilin II,…”

Section: Introductionmentioning

confidence: 99%

Endophilin isoforms have distinct characteristics in interactions with N-type Ca2+ channels and dynamin I

Tian¹,

Zhang²,

Fan

et al. 2012

Neurosci. Bull.

View full text Add to dashboard Cite

Objective Formation of the endophilin II-Ca 2+ channel complex is Ca 2+ -dependent in clathrin-mediated endocytosis. However, little is known about whether the other two endophilin isoforms have the same features. The present study aimed to investigate the characteristics of the interactions of all three isoforms with Ca 2+ channels and dynamin I. Methods N-type Ca 2+ channel C-terminal fragments (NCFs) synthesized with a 3 H-leucine-labeled kit, were incubated with endophilin-GST fusion proteins, followed by pull-down assay. Results were counted on a scintillation counter. In addition, the different endophilin isoforms were each co-transfected with dynamin I into 293T cells, followed by flow cytometry and co-immunoprecipitation assay. Immunostaining was performed and an image analysis program was used to evaluate the overlap coefficient of cells expressing endophilin and dynamin I. Results All three isoforms interacted with NCF. Endophilins I and II demonstrated clear Ca 2+ -dependent interactions with NCF, whereas endophilin III did not. Co-immunoprecipitation showed that, compared to endophilin I/II, the interaction between endophilin III and dynamin I was significantly increased. Similar results were obtained from flow cytometry. Furthermore, endophilin III had a higher overlap coefficient with dynamin I in co-transfected 293T cells. Conclusion Endophilin isoforms have distinct characteristics in interactions with NCF and dynamin I. Endophilin III binding to NCF is Ca 2+ -independent, implying that it plays a different role in clathrin-mediated endocytosis.

show abstract

Synaptojanin Is Recruited by Endophilin to Promote Synaptic Vesicle Uncoating

Cited by 371 publications

References 43 publications

Two synaptojanin 1 isoforms are recruited to clathrin-coated pits at different stages

Two synaptojanin 1 isoforms are recruited to clathrin-coated pits at different stages

Stoned B mediates sorting of integral synaptic vesicle proteins

Endophilin isoforms have distinct characteristics in interactions with N-type Ca2+ channels and dynamin I

Contact Info

Product

Resources

About