A presynaptic inositol-5-phosphatase

McPherson, Peter S.; Garcia, Elizabeth; Slepnev, Vladimir I.; David, Carol; Zhang, Xiaomei; Grabs, Detlev; Sossini, Wayne S.; Bauerfeind, Rudolf; Nemoto, Yasuo; Camilli, Pietro De

doi:10.1038/379353a0

Cited by 550 publications

(562 citation statements)

References 28 publications

Supporting

Mentioning

547

Contrasting

Order By: Relevance

“…Perhaps the Nmyristoylated ARF1 peptide was more potent in eliciting a phospholipase D activation relevant to TGN-derived secretory vesicle biogenesis than the N-myristoylated ARF4 peptide [33]. A role of phospholipase D in the biogenesis of TGNderived secretory vesicles would be consistent with the growing evidence implicating lipid modifications in the course of vesicle budding and fission [23,[34][35][36][37].…”

Section: Discussionmentioning

confidence: 61%

A role for ADP‐ribosylation factor 1, but not COP I, in secretory vesicle biogenesis from the trans‐Golgi network

Barr

Huttner

1996

FEBS Letters

View full text Add to dashboard Cite

A synthetic N-myristoylated peptide corresponding to the amino-terminal domain of ADP-ribosylation factor 1 (ARF1) markedly increases, in a cell-free system using post-nuclear supernatant from PC12 cells, the biogenesis of constitutive secretory vesicles and immature secretory granules from the trans-Goigi network (TGN). The related N-myristoylated ARF4 peptide only weakly stimulates, and the non-myristoylated ARF1 and ARF4 peptides inhibit, the biogenesis of these secretory vesicles. In a modified cell-free system using TGN membranes, eoatomer-depleted cytosol supports the biogenesis of TGNderived secretory vesicles to the same extent as control cytosol. These results suggest a role for ARF1, but not the COP I coat, in secretory vesicle biogenesis from the TGN, possibly via the activation of phospholipase D. [10,11], the biogenesis of both CSVs and ISGs, collectively referred to as TGN-derived secretory vesicles, is inhibited by brefeldin A. If one extrapolates from the observations on the formation of cis-Golgi-derived vesicles to the biogenesis of TGN-derived secretory vesicles, the inhibition by brefeldin A would be indicative of an involvement of ARF in the latter process [12]. In the present study, we have examined a possible role of ARF in the biogenesis of TGN-derived secretory vesicles. In addition, we have addressed the related question of whether or not coatomer is required for the biogenesis of these vesicles. Materials and methods

show abstract

Section: Discussionmentioning

confidence: 61%

A role for ADP‐ribosylation factor 1, but not COP I, in secretory vesicle biogenesis from the trans‐Golgi network

Barr

Huttner

1996

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…An abundant SH3 domain-containing protein, which is a major binding partner for dynamin I in nerve terminals (19), is amphiphysin, the dominant autoantigen in paraneoplastic stiff-man syndrome (20 -22). Amphiphysin is closely colocalized with dynamin I at synapses where, in addition to dynamin I, it binds the presynaptic inositol-5-phosphatase synaptojanin (23). Amphiphysin binds the plasmalemmal clathrin adaptor AP2 via a region distinct from its SH3 domain (19,24), further supporting an involvement of amphiphysin in endocytosis.…”

mentioning

confidence: 82%

The SH3 Domain of Amphiphysin Binds the Proline-rich Domain of Dynamin at a Single Site That Defines a New SH3 Binding Consensus Sequence

Grabs

Slepnev

Songyang

et al. 1997

Journal of Biological Chemistry

Self Cite

250

220

View full text Add to dashboard Cite

Amphiphysin is an SH3 domain-containing neuronal protein that is highly concentrated in nerve terminals where it interacts via its SH3 domain with dynamin I, a GTPase implicated in synaptic vesicle endocytosis. We show here that the SH3 domain of amphiphysin, but not a mutant SH3 domain, bound with high affinity to a single site in the long proline-rich region of human dynamin I, that this site was distinct from the binding sites for other SH3 domains, and that the mutation of two adjacent amino acids in dynamin I was sufficient to abolish binding. The dynamin I sequence critically required for amphiphysin binding (PSRPNR) fits in the novel SH3 binding consensus identified for the SH3 domain of amphiphysin via a combinatorial peptide library approach: PXRPXR(H)R(H). Our data demonstrate that the long proline-rich stretch present in dynamin I contained multiple SH3 domain binding sites that recognize interacting proteins with high specificity.Dynamin I is a neuronal GTPase concentrated in nerve terminals that plays an essential role in synaptic vesicle endocytosis and recycling (for reviews, see Refs. 1 and 2). A temperature-sensitive mutation in the dynamin I gene of Drosophila leads to rapid and massive block of synaptic vesicle endocytosis resulting in a paralytic phenotype (3-5). Ultrastructural studies have shown that dynamin I forms rings at the neck of clathrin-coated pits, and it has been hypothesized that a conformational change of the ring that correlates with GTP hydrolysis represents a key step leading to vesicle fission from the plasmalemma (6, 7). In addition, dynamin I has also been implicated in rapid endocytosis, a form of Ca 2ϩ -triggered endocytosis detectable by capacitance measurement in neuroendocrine cells (8). Dynamin isoforms (dynamin II and dynamin III) are expressed in non-neuronal cells (9 -11) where they are thought to play a general role in clathrin-mediated endocytosis (12, 13).The COOH-terminal region of dynamin I contains a 100-amino acid-long proline-rich domain (14), which undergoes regulation by protein phosphorylation and binds a variety of SH3 domains (13,(15)(16)(17)(18)). An abundant SH3 domain-containing protein, which is a major binding partner for dynamin I in nerve terminals (19), is amphiphysin, the dominant autoantigen in paraneoplastic stiff-man syndrome (20 -22). Amphiphysin is closely colocalized with dynamin I at synapses where, in addition to dynamin I, it binds the presynaptic inositol-5-phosphatase synaptojanin (23). Amphiphysin binds the plasmalemmal clathrin adaptor AP2 via a region distinct from its SH3 domain (19, 24), further supporting an involvement of amphiphysin in endocytosis. In addition, amphiphysin contains regions of similarity to two yeast proteins, Rvs167 and Rvs161 (20,25,26), which genetic studies have shown to be implicated both in endocytosis and in the function of the actin cytoskeleton (26,27).As a premise to further elucidate the functional interconnections between amphiphysin and dynamin I, we investigated regions that are crucial for re...

show abstract

“…I max is defined as the maximal inhibition of clathrin assembly. further interest that one of the appropriate 5-phosphatase activities can be catalyzed by synaptojanin, which is enriched in nerve terminals where AP-3 is also concentrated (23).…”

Section: Table I Constants For the Displacement Of Insp 6 From Gst-apmentioning

confidence: 99%

“…* acts with the Src homology 3 domain of Grb2 and amphiphysin and is rapidly dephosphorylated following synaptic activity (22)(23)(24). An essential role of inositides in neuronal secretion is also believed to account for the long-standing observation that ATP is essential for the priming of vesicles to be fusion competent (25).…”

mentioning

confidence: 99%

Regulation of AP-3 Function by Inositides

Hao

Tan

Prasad

et al. 1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

As part of the growing effort to understand the role inositol phosphates and inositol lipids play in the regulation of vesicle traffic within nerve terminals, we determined whether or not the synapse-specific clathrin assembly protein AP-3 can interact with inositol lipids. We found that soluble dioctanoyl-phosphatidylinositol 3,4,5-trisphosphate (DiC 8 PtdIns(3,4,5)P 3 ) was only 7.5-fold weaker a ligand than D-myo-inositol hexakisphosphate in assays that measured the displacement of D-myo-[3 H]inositol hexakisphosphate. In functional assays we found that both of these ligands inhibited clathrin assembly, but DiC 8 -PtdIns(3,4,5)P 3 was more potent and exhibited a larger maximal effect. We also examined the structural features of DiC 8 -PtdIns(3,4,5)P 3 that establish specificity. Dioctanoyl-phosphatidylinositol 3,4-bisphosphate, which does not have a 5-phosphate, and 4,5-O-bisphosphoryl-D-myo-inosityl 1-O-(1,2-O-diundecyl)-sn-3-glycerylphosphate, which does not have a 3-phosphate, were, respectively, 2-fold and 4-fold less potent than DiC 8 -PtdIns(3,4,5)P 3 as inhibitors of clathrin assembly. Deacylation of DiC 8 -PtdIns(3,4,5)P 3 reduced its affinity for AP-3 almost 20-fold, and also dramatically lowered its ability to inhibit clathrin assembly. The deacylated products of the soluble derivatives of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate were both not significant inhibitors of clathrin assembly. It therefore appears that the interactions of inositides with AP-3 should not be considered simply in terms of electrostatic effects of the highly charged phosphate groups. Ligand specificity appears also to be mediated by hydrophobic interactions with the fatty-acyl chains of the inositol lipids.There is increasing evidence that certain inositides (members of a large family of inositol phosphates and inositol lipids) act at several levels to regulate both the recruitment and the activation of proteins involved in vesicular transport. PtdIns(3,4,5)P 3 , 1 and the polyphosphoinositide 3-kinase that synthesizes this lipid both feature prominently in this area (1, 2). For example, intracellular trafficking of tyrosine kinase receptors depends upon interactions between the internalized receptors and the 3-kinase (3). Additionally, PtdIns(3,4,5)P 3 interacts either directly or indirectly with several GTPases that play important roles in vesicle traffic (1). Finally, in yeast, the Vps34 protein that is essential for Golgi to vacuole transport is a phosphoinositide 3-kinase (4).Interest in this field is not restricted to the inositol lipids. Other studies into the roles of the inositides in protein traffic have ascertained that certain inositol polyphosphates can bind with high affinity to the clathrin assembly proteins, AP-2 and AP-3 (5-9). AP-2 is believed to play a general role in endocytosis, since it has been found on vesicles budding from the plasma membranes of all types of cells (10). AP-3 is believed to play a more specialized role in synaptic vesicle biogenesis and recycling...

show abstract

A presynaptic inositol-5-phosphatase

Cited by 550 publications

References 28 publications

A role for ADP‐ribosylation factor 1, but not COP I, in secretory vesicle biogenesis from the trans‐Golgi network

A role for ADP‐ribosylation factor 1, but not COP I, in secretory vesicle biogenesis from the trans‐Golgi network

The SH3 Domain of Amphiphysin Binds the Proline-rich Domain of Dynamin at a Single Site That Defines a New SH3 Binding Consensus Sequence

Regulation of AP-3 Function by Inositides

Contact Info

Product

Resources

About