Matches in SemOpenAlex for { <https://semopenalex.org/work/W2556131490> ?p ?o ?g. }
Showing items 1 to 90 of
90
with 100 items per page.
- W2556131490 abstract "Abstract Abstract 382 Wiskott-Aldrich Syndrome (WAS) is an X-linked disorder associated with thrombocytopenia and is due to loss of function mutations in the Wiskott-Aldrich Syndrome Protein (WASP) gene. WASP serves to trigger actin nucleation upon its binding to activated form of Cdc42, phosphorylation by Src kinases, and membrane phospholipid. Loss of function mutations in WASP results in thrombocytopenia and small platelets, but the precise mechanism remains elusive. Using the Src kinase Lyn as bait in yeast two-hybrid screen, we isolated Cdc42 interaction protein 4 (CIP4). CIP4 is a member of the F-BAR family of proteins, which generate membrane curvature and promote cortical actin polymerization. CIP4 possesses an SH3 domain that almost exclusively interacts with WASP and Dynamin, a GTPase involved in membrane scission. To better understand the physiologic role of CIP4, we made the CIP4 knockout mouse strain. We have reported that these mice display defects in clathrin-dependent and clathrin-independent endocytosis (Feng et al J Biol Chem 285:4348, 2010). Because of CIP4's interaction with WASP, we hypothesized that there may be defects in platelet production. Complete blood counts performed on C57BL/6 male mice between the ages of 3 and 6 months showed a decrease in platelets in CIP4-/- mice comparable to that observed in WAS−/0 mice (Table 1). No other defects were observed in hemoglobin and total leukocyte, absolute neutrophil, and absolute lymphocyte counts. Mean platelet volume was normal in CIP4-/- as in WAS−/0 mice. Bone marrow examination showed no dysmorphology. There was no difference in numbers of CFU-MK, CFU-GEMM, or CFU-GM between CIP4-/- and wild-type mice. Since there are other cytoskeletal proteins that interact with WASP and may contribute to thrombocytopenia, we are currently generating CIP4, WASP double knockouts. Available data will be presented. Should the double knockout strain have the same degree of thrombocytopenia, this would strongly suggest that CIP4-WASP interaction constitutes the critical pathway for WASP-dependent platelet production. Propidium iodine staining of CD41+ bone marrow cells showed similar greater ploidy in wild-type than in CIP4-/-. Also, CIP4-/- megakaryocytes displayed fewer proplatet protrusions. Proplatelet protrusions are due to membrane remodeling and elongation due to actin and microtubule polymerization. This effect is similar to our observation of fewer invadopodia/MDA-MB-231 breast cancer cells. These findings suggest that CIP4 contributes to WASP-mediated thrombocytopenia by affecting membrane remodeling and protrusion stability. Since CIP4's ancestral protein Cdc15p is involved in the contractile actomyosin ring during cytokinesis in fission yeast, there may also be defects in endomitosis of the CIP4-deficient megakaryocyte. Table 1. Hematologic values WBC ANC ALC Hgb MCV Plt PV WT 17.5 ± 4 3.4 12.8 14 ± 2 43 ± 1 746 ± 97 4.6 CIP4-/- 17.8 ± 2 2.9 13.6 13.7 ± 3 46 ± 2 499 ± 77 4.7 WAS−/0 16.5 ± 3 2.6 12.7 12.3 ± 2 44 ± 1 457 ± 141 4.7 Disclosures: No relevant conflicts of interest to declare." @default.
- W2556131490 created "2016-11-30" @default.
- W2556131490 creator A5002935249 @default.
- W2556131490 creator A5006803661 @default.
- W2556131490 creator A5027470095 @default.
- W2556131490 creator A5031423349 @default.
- W2556131490 creator A5074867078 @default.
- W2556131490 date "2010-11-19" @default.
- W2556131490 modified "2023-09-27" @default.
- W2556131490 title "Loss of the WASP-Interacting Protein, CIP4, Results In Murine Thrombocytopenia: Insights Into the Pathophysiology of WASP-Related Thrombocytopenia" @default.
- W2556131490 doi "https://doi.org/10.1182/blood.v116.21.382.382" @default.
- W2556131490 hasPublicationYear "2010" @default.
- W2556131490 type Work @default.
- W2556131490 sameAs 2556131490 @default.
- W2556131490 citedByCount "1" @default.
- W2556131490 crossrefType "journal-article" @default.
- W2556131490 hasAuthorship W2556131490A5002935249 @default.
- W2556131490 hasAuthorship W2556131490A5006803661 @default.
- W2556131490 hasAuthorship W2556131490A5027470095 @default.
- W2556131490 hasAuthorship W2556131490A5031423349 @default.
- W2556131490 hasAuthorship W2556131490A5074867078 @default.
- W2556131490 hasConcept C104317684 @default.
- W2556131490 hasConcept C108636557 @default.
- W2556131490 hasConcept C142669718 @default.
- W2556131490 hasConcept C1491633281 @default.
- W2556131490 hasConcept C153911025 @default.
- W2556131490 hasConcept C170493617 @default.
- W2556131490 hasConcept C175818844 @default.
- W2556131490 hasConcept C184235292 @default.
- W2556131490 hasConcept C185592680 @default.
- W2556131490 hasConcept C203014093 @default.
- W2556131490 hasConcept C2780939953 @default.
- W2556131490 hasConcept C28005876 @default.
- W2556131490 hasConcept C2993400109 @default.
- W2556131490 hasConcept C42362537 @default.
- W2556131490 hasConcept C55493867 @default.
- W2556131490 hasConcept C55851684 @default.
- W2556131490 hasConcept C62478195 @default.
- W2556131490 hasConcept C86803240 @default.
- W2556131490 hasConcept C89560881 @default.
- W2556131490 hasConcept C90059517 @default.
- W2556131490 hasConcept C95444343 @default.
- W2556131490 hasConceptScore W2556131490C104317684 @default.
- W2556131490 hasConceptScore W2556131490C108636557 @default.
- W2556131490 hasConceptScore W2556131490C142669718 @default.
- W2556131490 hasConceptScore W2556131490C1491633281 @default.
- W2556131490 hasConceptScore W2556131490C153911025 @default.
- W2556131490 hasConceptScore W2556131490C170493617 @default.
- W2556131490 hasConceptScore W2556131490C175818844 @default.
- W2556131490 hasConceptScore W2556131490C184235292 @default.
- W2556131490 hasConceptScore W2556131490C185592680 @default.
- W2556131490 hasConceptScore W2556131490C203014093 @default.
- W2556131490 hasConceptScore W2556131490C2780939953 @default.
- W2556131490 hasConceptScore W2556131490C28005876 @default.
- W2556131490 hasConceptScore W2556131490C2993400109 @default.
- W2556131490 hasConceptScore W2556131490C42362537 @default.
- W2556131490 hasConceptScore W2556131490C55493867 @default.
- W2556131490 hasConceptScore W2556131490C55851684 @default.
- W2556131490 hasConceptScore W2556131490C62478195 @default.
- W2556131490 hasConceptScore W2556131490C86803240 @default.
- W2556131490 hasConceptScore W2556131490C89560881 @default.
- W2556131490 hasConceptScore W2556131490C90059517 @default.
- W2556131490 hasConceptScore W2556131490C95444343 @default.
- W2556131490 hasLocation W25561314901 @default.
- W2556131490 hasOpenAccess W2556131490 @default.
- W2556131490 hasPrimaryLocation W25561314901 @default.
- W2556131490 hasRelatedWork W1968743646 @default.
- W2556131490 hasRelatedWork W1979504896 @default.
- W2556131490 hasRelatedWork W2004945173 @default.
- W2556131490 hasRelatedWork W2011137086 @default.
- W2556131490 hasRelatedWork W2316529729 @default.
- W2556131490 hasRelatedWork W2532604109 @default.
- W2556131490 hasRelatedWork W2564125497 @default.
- W2556131490 hasRelatedWork W2567128047 @default.
- W2556131490 hasRelatedWork W2567271310 @default.
- W2556131490 hasRelatedWork W2575746863 @default.
- W2556131490 hasRelatedWork W2585726499 @default.
- W2556131490 hasRelatedWork W2589082674 @default.
- W2556131490 hasRelatedWork W2594062219 @default.
- W2556131490 hasRelatedWork W2736741004 @default.
- W2556131490 hasRelatedWork W2998847231 @default.
- W2556131490 hasRelatedWork W3024624807 @default.
- W2556131490 hasRelatedWork W3096796359 @default.
- W2556131490 hasRelatedWork W3139265103 @default.
- W2556131490 hasRelatedWork W3154276104 @default.
- W2556131490 hasRelatedWork W3192244938 @default.
- W2556131490 isParatext "false" @default.
- W2556131490 isRetracted "false" @default.
- W2556131490 magId "2556131490" @default.
- W2556131490 workType "article" @default.