Differential expression of wild-type and mutant NMMHC-IIA polypeptides in blood cells suggests cell-specific regulation mechanisms in MYH9 disorders

Blood
Shinji KunishimaHidehiko Saito

Abstract

MYH9 disorders such as May-Hegglin anomaly are characterized by macrothrombocytopenia and cytoplasmic granulocyte inclusion bodies that result from mutations in MYH9, the gene for nonmuscle myosin heavy chain-IIA (NMMHC-IIA). We examined the expression of mutant NMMHC-IIA polypeptide in peripheral blood cells from patients with MYH9 5770delG and 5818delG mutations. A specific antibody to mutant NMMHC-IIA (NT629) was raised against the abnormal carboxyl-terminal residues generated by 5818delG. NT629 reacted to recombinant 5818delG NMMHC-IIA but not to wild-type NMMHC-IIA, and did not recognize any cellular components of normal peripheral blood cells. Immunofluorescence and immunoblotting revealed that mutant NMMHC-IIA was present and sequestrated only in inclusion bodies within neutrophils, diffusely distributed throughout lymphocyte cytoplasm, sparsely localized on a diffuse cytoplasmic background in monocytes, and uniformly distributed at diminished levels only in large platelets. Mutant NMMHC-IIA did not translocate to lamellipodia in surface activated platelets. Wild-type NMMHC-IIA was homogeneously distributed among megakaryocytes derived from the peripheral blood CD34(+) cells of patients, but coarse mutant NMMHC-IIA was h...Continue Reading

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Citations

Oct 24, 2009·Nature Reviews. Molecular Cell Biology·Miguel Vicente-ManzanaresAlan Rick Horwitz
Jul 6, 2010·Current Opinion in Hematology·Shinji Kunishima, Hidehiko Saito
Dec 5, 2012·Acta Haematologica·Xiong-hua SunChang-geng Ruan
Aug 5, 2008·Thrombosis Research·Rachel A BurtBenjamin T Kile
Oct 17, 2015·Blood·Shinji KunishimaRyoji Kobayashi
Jan 21, 2016·Blood·Koji Eto, Shinji Kunishima
Feb 5, 2009·European Journal of Haematology·Yuji Miyajima, Shinji Kunishima
Jul 12, 2008·European Journal of Haematology·Shinji KunishimaHidehiko Saito
Nov 18, 2010·Cell Biology International·Decivaldo dos Santos DiasMilton Vieira Coelho
May 29, 2012·Pediatrics International : Official Journal of the Japan Pediatric Society·Tomomi UyedaShinji Kunishima
Jun 10, 2015·Journal of Pediatric Hematology/oncology·Satomi OkanoShinji Kunishima
Feb 21, 2008·European Journal of Haematology·Shinji KunishimaHidehiko Saito
May 6, 2011·British Journal of Haematology·Carlo L BalduiniAnna Savoia
Sep 4, 2009·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Neeraj SinghRocco C Venuto

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