Myosin vb

The membrane (M) glycoprotein of coronaviruses (CoVs) serves as the nidus for virion assembly. Using a yeast two-hybrid screen, we identified the interaction of the cytosolic tail of Murine Hepatitis Virus (MHV-CoV) M protein with Myosin Vb (MYO5B), specifically with the alternative splice variant of cellular MYO5B including exon D (MYO5B+D), which mediates interaction with Rab10. When co-expressed in human lung epithelial A549 and canine kidney epithelial MDCK cells, MYO5B+D co-localized with the MHV-CoV M protein, as well as with the M proteins from Porcine Epidemic Diarrhea Virus (PEDV-CoV), Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome 2 (SARS-CoV-2)...

BACKGROUND: Pelvic floor muscle injury is a common consequence of vaginal childbirth. Nonsteroidal anti-inflammatory drugs are widely used postpartum analgesics. Multiple studies have reported negative effects of these drugs on limb muscle regeneration, but their impact on pelvic floor muscle recovery following birth injury has not been explored. OBJECTIVE: Using a validated rat model, we assessed the effects of nonsteroidal anti-inflammatory drug on acute and longer-term pelvic floor muscle recovery following simulated birth injury...

Microvillus Inclusion Disease (MVID), caused by loss-of-function mutations in the motor protein Myosin Vb (MYO5B), is a severe infantile disease characterized by diarrhea, malabsorption, and acid-base instability, requiring intensive parenteral support for nutritional and fluid management. Human patient-derived enteroids represent a model for investigation of monogenic epithelial disorders but are a rare resource from MVID patients. We developed human enteroids with different loss-of function MYO5B variants and showed that they recapitulated the structural changes found in native MVID enterocytes...

The upsurge of bacterial resistance to conventional antibiotics turned a well-recognized public health threat. The need of developing new biomaterials of effective practical use in order to tackle bacterial resistance became urgent. In this study, a submicrometric bioparticle of known antibacterial activity was produced in powder form with suitable texture and appealing characteristics for effective oral administration. Through complex coacervating a natural-source antimicrobial polypeptide with chitosan-N-arginine and alginate, the bioactive polypeptide was physically incorporated to the bioparticle whose structure positively responds to the pH variations found in gastrointestinal tract...

The external urethral sphincter (EUS) is crucial in urinary continence development. Understanding the morphological features of the EUS in female rats after vaginal distention (VD), using a model of birth trauma, would aid in evaluating its functional and metabolic properties. Our recent study demonstrated that the EUS in female rats expresses one slow (type 1) and two fast (types 2A and 2B) myosin heavy chain (MHC) isoforms. Our preliminary experiment revealed that type 2B isoform expression was markedly reduced in the EUS 4 weeks after VD...

Smooth muscle cells contribute to the mechanical function of various soft tissues, however, their contribution to the viscoelastic response when subjected to multiaxial loading remains unknown. The vagina is a fibromuscular viscoelastic organ that is exposed to prolonged and increased pressures with daily activities and physiologic processes such as vaginal birth. The vagina changes in geometry over time under prolonged pressure, known as creep. Vaginal smooth muscle cells may contribute to creep. This may be critical for the function of vaginal and other soft tissues that experience fluctuations in their biomechanical environment...

UNLABELLED: Microvillus Inclusion Disease (MVID), caused by loss-of-function mutations in the motor protein Myosin Vb (MYO5B), is a severe infantile disease characterized by diarrhea, malabsorption, and acid-base instability, requiring intensive parenteral support for nutritional and fluid management. Human patient-derived enteroids represent a model for investigation of monogenic epithelial disorders but are a rare resource from MVID patients. We developed human enteroids with different loss-of function MYO5B variants and showed that they recapitulated the structural changes found in native MVID enterocytes...

Vesicle trafficking has emerged as an important process driving tumor progression through various mechanisms. Transforming growth factor beta (TGFβ)-mediated secretion of Angiopoietin-like 4 (ANGPTL4) is important for cancer development. Here, Formin-like 2 (FMNL2) is identified to be necessary for ANGPTL4 trafficking and secretion in response to TGFβ. Protein kinase C (PKC)-dependent phosphorylation of FMNL2 downstream of TGFβ stimulation is required for cancer cell invasion as well as ANGPTL4 vesicle trafficking and secretion...

Carcinoma of the endometrium of the uterus is the most common female pelvic malignancy. Although uterine corpus endometrial cancer (UCEC) has a favorable prognosis if removed early, patients with advanced tumor stages have a low survival rate. These facts highlight the importance of understanding UCEC biology. Computational analysis of RNA-sequencing data from UCEC patients revealed that the molecular motor Myosin Vb (MYO5B) was elevated in the beginning stages of UCEC and occurred in all patients regardless of tumor stage, tumor type, age, menopause status or ethnicity...

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Colorectal cancer causes >900,000 deaths every year and a deeper understanding of the molecular mechanisms underlying this disease will contribute to improve its clinical management and survival. Myosin Vb (MYO5B) regulates intracellular vesicle trafficking, and inactivation of this myosin disrupts the polarization and differentiation of intestinal epithelial cells causing microvillous inclusion disease (MVID), a rare congenital disorder characterized by intractable life-threatening diarrhea. Here, we show that the loss Myosin Vb interfered with the differentiation/polarization of colorectal cancer cells...

Microvillus inclusion disease (MVID), a lethal congenital diarrheal disease, results from loss of function mutations in the apical actin motor myosin VB (MYO5B). How loss of MYO5B leads to both malabsorption and fluid secretion is not well understood. Serum glucocorticoid-inducible kinase 1 (SGK1) regulates intestinal carbohydrate and ion transporters including cystic fibrosis transmembrane conductance regulator (CFTR). We hypothesized that loss of SGK1 could reduce CFTR fluid secretion and MVID diarrhea. Using CRISPR-Cas9 approaches, we generated R26Cre ER;MYO5Bf/f conditional single knockout (cMYO5BKO) and R26Cre ER;MYO5Bf/f ;SGK1f/f double knockout (cSGK1/MYO5B-DKO) mice...

Inherited diarrheal disorders cause serious morbidity resulting in dependence on intensive care and parenteral nutrition. Microvillus inclusion disease (MVID) has been classically described and results from mutations in the gene coding myosin Vb, which is responsible for enterocyte polarization. Newer reports of mutations resulting in truncated syntaxin 3 (STX3) and Munc18-2 (STXBP2) proteins have been elucidated as causative. To date, five cases of STX3 abnormalities resulting in MVID have been described. We report an infant who presented with congenital diarrhea and was determined to have a rare mutation of STX3...

Microvillus inclusion disease (MVID) is a congenital diarrheal disorder resulting in life-threatening secretory diarrhea in newborns. Inactivating and nonsense mutations in myosin Vb (MYO5B) have been identified in MVID patients. Work using patient tissues, cell lines, mice, and pigs has led to critical insights into the pathology of MVID and a better understanding of both apical trafficking in intestinal enterocytes and intestinal stem cell differentiation. These studies have demonstrated that loss of MYO5B or inactivating mutations lead to loss of apical sodium and water transporters, without loss of apical CFTR, accounting for the major pathology of the disease...

Variants in the UNC45A cochaperone have been recently associated with a syndrome combining diarrhea, cholestasis, deafness, and bone fragility. Yet the mechanism underlying intestinal failure in UNC45A deficiency remains unclear. Here, biallelic variants in UNC45A were identified by next-generation sequencing in 6 patients with congenital diarrhea. Corroborating in silico prediction, variants either abolished UNC45A expression or altered protein conformation. Myosin VB was identified by mass spectrometry as client of the UNC45A chaperone and was found misfolded in UNC45AKO Caco-2 cells...

BACKGROUND: Bile is an important liver secretion which aids the digestion of fats in the intestine. Bile acids are the major organic solute component of bile and are synthesized from cholesterol in the liver and stored in the gallbladder. After secretion in the intestine, bile acids are re-absorbed in the distal small intestine (ileum). Imbalances in the reabsorption of bile acids can lead to bile acid diarrhea when bile acid malabsorption occurs. Conversely, when there is an increase in bile acid absorption hepatic disorders such as nonalcoholic fatty liver disease can arise...

BACKGROUND: Intestinal goblet cells secrete a protective mucus layer preventing bacteria and harmful ingested substances from contacting the columnar epithelial cells that line the intestine. Single cell RNAseq data has revealed that goblet cells have high expression of Myosin 5b (Myo5b), a molecular motor that regulates vesicle trafficking in epithelial cells. Myo5b is most widely studied in the small intestine, but it's role in the colonic epithelium and particularly goblet cells is unknown...

Microvillus Inclusion Disease (MVID) is a lethal congenital diarrheal disease resulting from loss of function mutations in the actin motor myosin VB (MYO5B) that regulates apical traffic. MVID remains without treatment to reverse the severe diarrhea that leads to death. MVID diarrhea results from both increased fluid secretion and malabsorption of ions and carbohydrates in the small intestine. Serum and Glucocorticoid-inducible kinase 1 (SGK1), is a potent regulator of ion transporters including cystic fibrosis transmembrane conductance regulator (CFTR) in the intestine...

The membrane (M) glycoprotein of coronaviruses (CoVs) serves as the nidus for virion assembly. Using a yeast two-hybrid screen, we identified the interaction of the cytosolic tail of Murine Hepatitis Virus (MHV-CoV) M protein with Myosin Vb (MYO5B) (Figure 1A). MHV-CoV M interacts specifically with the alternative splice variant of cellular MYO5B including Exon D (MYO5B+D), that also mediates interaction with cellular Rab10. When co-expressed in human lung epithelial A549 and canine kidney epithelial MDCK cells, MYO5B+D co-localized with MHV-CoV M protein, as well as with M proteins from porcine epidemic diarrhea Virus (PEDV-CoV), Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) (Figure 2)...

BACKGROUND AND AIMS: Differentiation of intestinal epithelial cells involves cell division inhibition, cell lineage choice, and brush border elaboration. Myosin Vb (MYO5B) is a motor protein that is critical for cell polarization and membrane protein trafficking in intestinal epithelial cells and its deficiency causes both hyperproliferation and microvillus defects. Recently, we reported that a bioactive phospholipid, lysophosphatidic acid (LPA), can promote cell differentiation and nutrient absorption in tamoxifen-induced MYO5B knockout mice in vivo and in enteroids...