Synaptojanin 2, a novel Rac1 effector that regulates clathrin-mediated endocytosis

Malecz, Nicole; McCabe, Peter C.; Spaargaren, Caroline; Qiu, Rong-Guo; Chuang, Ya-yu; Symons, Marc

doi:10.1016/s0960-9822(00)00778-8

Cited by 131 publications

(119 citation statements)

References 13 publications

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“…However, expression of dominant-negative mutants of these signalling proteins had no effect on receptor uptake in intact cells, suggesting that the observed effects of constitutively active Rac and RhoA may be an indirect consequence of locking these proteins in the active conformation. Symons and co-workers [50] have extended these studies by showing that activated Rac binds directly to the PtdIns(4,5)P # phosphatase synaptojanin 2 and recruits it to cell membranes. Localized concentrations of PtdIns(4,5)P # act as nucleation sites for endocytosis at the plasma membrane, recruiting clathrin and accessory proteins [51].…”

Section: Rhoa and Racmentioning

confidence: 95%

“…After internalization, PtdIns(4,5)P # on clathrin-coated vesicles is hydrolysed by synaptojanin, allowing uncoating of the vesicle and the formation of early endosomes [52]. Fusion of synaptojanin to a membrane targeting motif blocks epidermal-growth-factor (EGF)-receptor internalization [50], suggesting that constitutively active mutants of Rac may block endocytosis by recruiting synaptojanin to the plasma membrane and depleting PtdIns(4,5)P # at endocytic sites -but what does this say about how Rac acts in i o ? Rac is also able to stimulate synthesis of PtdIns(4,5)P # through activation of type I PtdIns4P 5-kinases [18,53].…”

Section: Rhoa and Racmentioning

confidence: 99%

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Regulation of endocytic traffic by Rho GTPases

Qualmann

Mellor

2003

Biochemical Journal

116

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The members of the Rho subfamily of small GTPases are key regulators of the actin cytoskeleton. However, recent studies have provided evidence for multiple additional roles for these signalling proteins in controlling endocytic traffic. Here we review our current understanding of Rho GTPase action within the endocytic pathway and examine the potential points of convergence with the more established, actin-based functions of these signalling proteins.

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Section: Rhoa and Racmentioning

confidence: 95%

Section: Rhoa and Racmentioning

confidence: 99%

Regulation of endocytic traffic by Rho GTPases

Qualmann

Mellor

2003

Biochemical Journal

116

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“…There is a correlation in both time and space between the formation of endocytic vesicles and the reorganization of the actin cytoskeleton (107,214,327,380,382). In S. cerevisiae, where clathrin is not required for endocytosis, actin plays a crucial role (245).…”

Section: A Ptdins(45)p 2 At the Plasma Membranementioning

confidence: 99%

Phosphoinositides in Constitutive Membrane Traffic

Roth

2004

Physiological Reviews

265

267

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Proteins that make, consume, and bind to phosphoinositides are important for constitutive membrane traffic. Different phosphoinositides are concentrated in different parts of the central vacuolar pathway, with phosphatidylinositol 4-phosphate predominate on Golgi, phosphatidylinositol 4,5-bisphosphate predominate at the plasma membrane, phosphatidylinositol 3-phosphate the major phosphoinositide on early endosomes, and phosphatidylinositol 3,5-bisphosphate found on late endocytic organelles. This spatial segregation may be the mechanism by which the direction of membrane traffic is controlled. Phosphoinositides increase the affinity of membranes for peripheral membrane proteins that function for sorting protein cargo or for the docking and fusion of transport vesicles. This implies that constitutive membrane traffic may be regulated by the mechanisms that control the activity of the enzymes that produce and consume phosphoinositides. Although the lipid kinases and phosphatases that function in constitutive membrane traffic are beginning to be identified, their regulation is poorly understood.

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“…Next, proteins were blotted on nitrocellulose membranes and the presence of Syn 2 was shown using specific polyclonal antibodies. 21 binding to such proteins both Syn 1 and Syn 2 probably are involved in various normal and pathogenic pathways. By binding to Grb-2, a member of a family of adaptor proteins that couple receptor tyrosine kinases to the Ras signaling pathway, Syn 2 plays an important role in regulating actin filaments by controlling PtdIns 4,5-P2 levels bound to cytoskeleton-regulating molecules.…”

Section: Discussionmentioning

confidence: 99%

“…Syn 2 was visualized by the Syn 2-specific polyclonal Ab, 21 kindly provided by Dr M Symon (Onyx Pharmaceuticals, Richmond, CA, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

Synaptojanin 2 is recognized by HLA class II-restricted hairy cell leukemia-specific T cells

et al. 2003

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Hairy cell leukemia (HCL) is a chronic mature B-cell leukemia characterized by malignant B cells that have typical hairy protrusions. To characterize possible HCL-associated tumor antigens, we generated an HCL-specific and HLA class II (DPw4)-restricted proliferative CD4 þ T-cell clone. To identify the target antigen of these T cells, we constructed a synthetic peptide library dedicated to bind HLA DPw4, and identified a mimicry epitope recognized by the T-cell clone. With this epitope, the recognition motif of the T-cell clone was deduced and a peptide of human synaptojanin 2 (Syn 2) was identified that stimulated the HCL-reactive T-cell clone. Both Northern and Western blot analyses showed that Syn 2 expression was increased in HCL samples compared to other B cells. Besides, the Syn 2-expressing cell line AML193, with the introduced restrictive HLA-DPw4 molecules, was recognized by the HCLspecific T-cell clone. These results indicate that Syn 2 is a target of autoreactive HCL-specific T cells. Since Syn 2 is a phosphatidylinositol 4,5-biphosphatase involved in cell growth and rearrangement of actin filaments, the increased Syn 2 expression may correlate with the disease etiology or the characteristic morphologic alterations caused by the disease.

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Synaptojanin 2, a novel Rac1 effector that regulates clathrin-mediated endocytosis

Cited by 131 publications

References 13 publications

Regulation of endocytic traffic by Rho GTPases

Regulation of endocytic traffic by Rho GTPases

Phosphoinositides in Constitutive Membrane Traffic

Synaptojanin 2 is recognized by HLA class II-restricted hairy cell leukemia-specific T cells

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