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Myosin vb

Ying-Yu Zhang, Zhen-Yan Fu, Jian Wei, Wei Qi, Gulinaer Baituola, Jie Luo, Ya-Jie Meng, Shu-Yuan Guo, Huiyong Yin, Shi-You Jiang, Yun-Feng Li, Hong-Hua Miao, Yong Liu, Yan Wang, Bo-Liang Li, Yi-Tong Ma, Bao-Liang Song
A high concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease. Although LDL-C levels vary among humans and are heritable, the genetic factors affecting LDL-C are not fully characterized. We identified a rare frameshift variant in the LIMA1 (also known as EPLIN or SREBP3 ) gene from a Chinese family of Kazakh ethnicity with inherited low LDL-C and reduced cholesterol absorption. In a mouse model, LIMA1 was mainly expressed in the small intestine and localized on the brush border membrane...
June 8, 2018: Science
Antonio Real-Hohn, D William Provance, Rafael Braga Gonçalves, Caio Bidueira Denani, Andréa Cheble de Oliveira, Verônica P Salerno, Andre Marco Oliveira Gomes
Together, the three human rhinovirus (RV) species are the most frequent cause of the common cold. Because of their high similarity with other viral species of the genus Enterovirus, within the large family Picornaviridae, studies on RV infectious activities often offer a less pathogenic model for more aggressive enteroviruses, e.g. poliovirus or EV71. Picornaviruses enter via receptor mediated endocytosis and replicate in the cytosol. Most of them depend on functional F-actin, Rab proteins, and probably motor proteins...
December 7, 2017: Scientific Reports
Elisabeth Letellier, Martine Schmitz, Aurélien Ginolhac, Fabien Rodriguez, Pit Ullmann, Komal Qureshi-Baig, Sonia Frasquilho, Laurent Antunes, Serge Haan
BACKGROUND: Selecting the most beneficial treatment regimens for colorectal cancer (CRC) patients remains challenging due to a lack of prognostic markers. Members of the Myosin family, proteins recognised to have a major role in trafficking and polarisation of cells, have recently been reported to be closely associated with several types of cancer and might thus serve as potential prognostic markers in the context of CRC. METHODS: We used a previously established meta-analysis of publicly available gene expression data to analyse the expression of different members of the Myosin V family, namely MYO5A, 5B, and 5C, in CRC...
November 21, 2017: British Journal of Cancer
Liam P Cheeseman, Jérôme Boulanger, Lisa M Bond, Melina Schuh
An egg must be fertilized by a single sperm only. To prevent polyspermy, the zona pellucida, a structure that surrounds mammalian eggs, becomes impermeable upon fertilization, preventing the entry of further sperm. The structural changes in the zona upon fertilization are driven by the exocytosis of cortical granules. These translocate from the oocyte's centre to the plasma membrane during meiosis. However, very little is known about the mechanism of cortical granule translocation. Here we investigate cortical granule transport and dynamics in live mammalian oocytes by using Rab27a as a marker...
December 19, 2016: Nature Communications
Jaydeep Sidhaye, Clyde Savio Pinto, Shweta Dharap, Tressa Jacob, Shobha Bhargava, Mahendra Sonawane
Microvillus inclusion disease (MVID) is a life-threatening enteropathy characterised by malabsorption and incapacitating fluid loss due to chronic diarrhoea. Histological analysis has revealed that enterocytes in MVID patients exhibit reduction of microvilli, presence of microvillus inclusion bodies and intestinal villus atrophy, whereas genetic linkage analysis has identified mutations in myosin Vb gene as the main cause of MVID. In order to understand the cellular basis of MVID and the associated formation of inclusion bodies, an animal model that develops ex utero and is tractable genetically as well as by microscopy would be highly useful...
November 2016: Mechanisms of Development
Dmitri V Kravtsov, Md Kaimul Ahsan, Vandana Kumari, Sven C D van Ijzendoorn, Miguel Reyes-Mugica, Anoop Kumar, Tarunmeet Gujral, Pradeep K Dudeja, Nadia A Ameen
Loss of function mutations in the actin motor myosin Vb (Myo5b) lead to microvillus inclusion disease (MVID) and death in newborns and children. MVID results in secretory diarrhea, brush border (BB) defects, villus atrophy, and microvillus inclusions (MVIs) in enterocytes. How loss of Myo5b results in increased stool loss of chloride (Cl(-)) and sodium (Na(+)) is unknown. The present study used Myo5b loss-of-function human MVID intestine, polarized intestinal cell models of secretory crypt (T84) and villus resembling (CaCo2BBe, C2BBe) enterocytes lacking Myo5b in conjunction with immunofluorescence confocal stimulated emission depletion (gSTED) imaging, immunohistochemical staining, transmission electron microscopy, shRNA silencing, immunoblots, and electrophysiological approaches to examine the distribution, expression, and function of the major BB ion transporters NHE3 (Na(+)), CFTR (Cl(-)), and SLC26A3 (DRA) (Cl(-)/HCO3 (-)) that control intestinal fluid transport...
July 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Arnab Gupta, Michael J Schell, Ashima Bhattacharjee, Svetlana Lutsenko, Ann L Hubbard
The cellular machinery responsible for Cu(+)-stimulated delivery of the Wilson-disease-associated protein ATP7B to the apical domain of hepatocytes is poorly understood. We demonstrate that myosin Vb regulates the Cu(+)-stimulated delivery of ATP7B to the apical domain of polarized hepatic cells, and that disruption of the ATP7B-myosin Vb interaction reduces the apical surface expression of ATP7B. Overexpression of the myosin Vb tail, which competes for binding of subapical cargos to myosin Vb bound to subapical actin, disrupted the surface expression of ATP7B, leading to reduced cellular Cu(+) export...
March 15, 2016: Journal of Cell Science
Agathe Chaigne, Clément Campillo, Raphaël Voituriez, Nir S Gov, Cécile Sykes, Marie-Hélène Verlhac, Marie-Emilie Terret
Mitotic spindle position relies on interactions between astral microtubules nucleated by centrosomes and a rigid cortex. Some cells, such as mouse oocytes, do not possess centrosomes and astral microtubules. These cells rely only on actin and on a soft cortex to position their spindle off-centre and undergo asymmetric divisions. While the first mouse embryonic division also occurs in the absence of centrosomes, it is symmetric and not much is known on how the spindle is positioned at the exact cell centre. Using interdisciplinary approaches, we demonstrate that zygotic spindle positioning follows a three-step process: (1) coarse centring of pronuclei relying on the dynamics of an F-actin/Myosin-Vb meshwork; (2) fine centring of the metaphase plate depending on a high cortical tension; (3) passive maintenance at the cell centre...
2016: Nature Communications
Leandro T Oliveira, Gabbriela V O Leon, D William Provance, Fernando G de Mello, Martha M Sorenson, Verônica P Salerno
Aging represents a major risk factor for numerous illnesses that are of increasing importance to society, including two of the most prevalent: diabetes and Alzheimer's disease. Studies have shown that diabetes is a risk factor for spontaneous Alzheimer's disease. While these studies suggest that diabetes can contribute to Alzheimer's disease, the implications of AD on diabetes are practically unexplored. The major mediator of the pathophysiological effects, the Aβ42 peptide, has been shown to enter neurons and lead to an alteration of the intracellular distribution of the molecular motor myosin Vb...
July 30, 2015: Brain Research
Andrew J Lindsay, Stéphanie Miserey-Lenkei, Bruno Goud
Myosins are actin-based motor proteins that are involved in a wide variety of cellular processes such as membrane transport, muscle contraction, and cell division. Humans have over 40 myosins that can be placed into 18 classes, the malfunctioning of a number of which can lead to disease. There are three members of the human class V myosin family, myosins Va, Vb, and Vc. People lacking functional myosin Va suffer from a rare autosomal recessive disease called Griscelli's Syndrome type I (GS1) that is characterized by severe neurological defects and partial albinism...
2015: Methods in Molecular Biology
Maria Almonacid, Wylie W Ahmed, Matthias Bussonnier, Philippe Mailly, Timo Betz, Raphaël Voituriez, Nir S Gov, Marie-Hélène Verlhac
In somatic cells, the position of the cell centroid is dictated by the centrosome. The centrosome is instrumental in nucleus positioning, the two structures being physically connected. Mouse oocytes have no centrosomes, yet harbour centrally located nuclei. We demonstrate how oocytes define their geometric centre in the absence of centrosomes. Using live imaging of oocytes, knockout for the formin 2 actin nucleator, with off-centred nuclei, together with optical trapping and modelling, we discover an unprecedented mode of nucleus positioning...
April 2015: Nature Cell Biology
Tomoaki Sobajima, Shin-Ichiro Yoshimura, Tomohiko Iwano, Masataka Kunii, Masahiko Watanabe, Nur Atik, Sotaro Mushiake, Eiichi Morii, Yoshihisa Koyama, Eiji Miyoshi, Akihiro Harada
The small GTPase Rab11 plays an important role in the recycling of proteins to the plasma membrane as well as in polarised transport in epithelial cells and neurons. We generated conditional knockout mice deficient in Rab11a. Rab11a-deficient mice are embryonic lethal, and brain-specific Rab11a knockout mice show no overt abnormalities in brain architecture. In contrast, intestine-specific Rab11a knockout mice begin dying approximately 1 week after birth. Apical proteins in the intestines of knockout mice accumulate in the cytoplasm and mislocalise to the basolateral plasma membrane, whereas the localisation of basolateral proteins is unaffected...
2014: Biology Open
Pang-Yu Hsueh, Maria C Edman, Guoyong Sun, Pu Shi, Shi Xu, Yi-An Lin, Honggang Cui, Sarah F Hamm-Alvarez, J Andrew MacKay
Rapid clearance from the tears presents a formidable obstacle to the delivery of peptide drugs to the eye surface. This impedes therapies for ocular infections, wound healing, and dry-eye disease that affect the vision of millions worldwide. To overcome this challenge, this manuscript explores a novel strategy to reach the ocular surface via receptor-mediated transcytosis across the lacrimal gland (LG), which produces the bulk of human tears. The LG abundantly expresses the coxsackievirus and adenovirus receptor (CAR); furthermore, we recently reported a peptide-based nanoparticle (KSI) that targets CAR on liver cells...
June 28, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
Jarred J Bultema, Judith A Boyle, Parker B Malenke, Faye E Martin, Esteban C Dell'Angelica, Richard E Cheney, Santiago M Di Pietro
Class V myosins are actin-based motors with conserved functions in vesicle and organelle trafficking. Herein we report the discovery of a function for Myosin Vc in melanosome biogenesis as an effector of melanosome-associated Rab GTPases. We isolated Myosin Vc in a yeast two-hybrid screening for proteins that interact with Rab38, a Rab protein involved in the biogenesis of melanosomes and other lysosome-related organelles. Rab38 and its close homolog Rab32 bind to Myosin Vc but not to Myosin Va or Myosin Vb...
November 28, 2014: Journal of Biological Chemistry
Dmitri Kravtsov, Anastasia Mashukova, Radia Forteza, Maria M Rodriguez, Nadia A Ameen, Pedro J Salas
Microvillus inclusion disease (MVID) is an autosomal recessive condition resulting in intractable secretory diarrhea in newborns due to loss-of-function mutations in myosin Vb (Myo5b). Previous work suggested that the apical recycling endosomal (ARE) compartment is the primary location for phosphoinositide-dependent protein kinase 1 (PDK1) signaling. Because the ARE is disrupted in MVID, we tested the hypothesis that polarized signaling is affected by Myo5b dysfunction. Subcellular distribution of PDK1 was analyzed in human enterocytes from MVID/control patients by immunocytochemistry...
November 15, 2014: American Journal of Physiology. Gastrointestinal and Liver Physiology
Sonal, Jaydeep Sidhaye, Mandar Phatak, Shamik Banerjee, Aditya Mulay, Ojas Deshpande, Sourabh Bhide, Tressa Jacob, Ines Gehring, Christiane Nuesslein-Volhard, Mahendra Sonawane
The epidermis is a stratified epithelium, which forms a barrier to maintain the internal milieu in metazoans. Being the outermost tissue, growth of the epidermis has to be strictly coordinated with the growth of the embryo. The key parameters that determine tissue growth are cell number and cell size. So far, it has remained unclear how the size of epidermal cells is maintained and whether it contributes towards epidermal homeostasis. We have used genetic analysis in combination with cellular imaging to show that zebrafish goosepimples/myosin Vb regulates plasma membrane homeostasis and is involved in maintenance of cell size in the periderm, the outermost epidermal layer...
September 2014: PLoS Genetics
Cornelia Thoeni, Ernest Cutz
MVID, first reported in 1972 as a familial enteropathy is a congenital disorder of intestinal mucosa characterized by villous atrophy with marked abnormalities of enterocytes which on electron microscopy (EM) show loss of apical microvilli, intracytoplasmic microvillous inclusions as well as vesicular inclusion bodies and subapical secretory-like granules. The clinical manifestations include severe malabsorption and intractable watery diarrhea starting at birth (classical MVID) or at few days or weeks of age (variant MVID)...
October 2014: Pathology
Byron C Knowles, Joseph T Roland, Moorthy Krishnan, Matthew J Tyska, Lynne A Lapierre, Paul S Dickman, James R Goldenring, Mitchell D Shub
Microvillus inclusion disease (MVID) is a severe form of congenital diarrhea that arises from inactivating mutations in the gene encoding myosin Vb (MYO5B). We have examined the association of mutations in MYO5B and disruption of microvillar assembly and polarity in enterocytes. Stable MYO5B knockdown (MYO5B-KD) in CaCo2-BBE cells elicited loss of microvilli, alterations in junctional claudins, and disruption of apical and basolateral trafficking; however, no microvillus inclusions were observed in MYO5B-KD cells...
July 2014: Journal of Clinical Investigation
Caroline L Wiegerinck, Andreas R Janecke, Kerstin Schneeberger, Georg F Vogel, Désirée Y van Haaften-Visser, Johanna C Escher, Rüdiger Adam, Cornelia E Thöni, Kristian Pfaller, Alexander J Jordan, Cleo-Aron Weis, Isaac J Nijman, Glen R Monroe, Peter M van Hasselt, Ernest Cutz, Judith Klumperman, Hans Clevers, Edward E S Nieuwenhuis, Roderick H J Houwen, Gijs van Haaften, Michael W Hess, Lukas A Huber, Janneke M Stapelbroek, Thomas Müller, Sabine Middendorp
Microvillus inclusion disease (MVID) is a disorder of intestinal epithelial differentiation characterized by life-threatening intractable diarrhea. MVID can be diagnosed based on loss of microvilli, microvillus inclusions, and accumulation of subapical vesicles. Most patients with MVID have mutations in myosin Vb that cause defects in recycling of apical vesicles. Whole-exome sequencing of DNA from patients with variant MVID showed homozygous truncating mutations in syntaxin 3 (STX3). STX3 is an apical receptor involved in membrane fusion of apical vesicles in enterocytes...
July 2014: Gastroenterology
László Homolya, Dong Fu, Prabuddha Sengupta, Michal Jarnik, Jean-Pierre Gillet, Lynn Vitale-Cross, J Silvio Gutkind, Jennifer Lippincott-Schwartz, Irwin M Arias
Polarization of hepatocytes is manifested by bile canalicular network formation and activation of LKB1 and AMPK, which control cellular energy metabolism. The bile acid, taurocholate, also regulates development of the canalicular network through activation of AMPK. In the present study, we used collagen sandwich hepatocyte cultures from control and liver-specific LKB1 knockout mice to examine the role of LKB1 in trafficking of ABCB11, the canalicular bile acid transporter. In polarized hepatocytes, ABCB11 traffics from Golgi to the apical plasma membrane and endogenously cycles through the rab 11a-myosin Vb recycling endosomal system...
2014: PloS One
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