Myosin VI is required for maintenance of brush border structure, composition, and membrane trafficking functions in the intestinal epithelial cell.
Characterization of the intestinal epithelium of the Snell's waltzer (sv/sv) mouse revealed that myosin VI (Myo6) is required for proper brush border (BB) ultrastructure, composition and membrane traffic. The defects observed were distinct from that observed in the myosin Ia KO, even though Myo6 is lost from the BB in this KO. Myo6 is expressed throughout the length of the small and large intestine; it is localized to the subapical inter-microvillar (MV) domain and basolateral membrane. Defects in the BB include apparent lifting of the plasma membrane off of the actin cytoskeleton in the inter-MV region, fusion of MV, and disorganized morphology of the terminal web. The molecular composition of the sv/sv BB is altered. This includes increased expression of myosin Va, myosin Ie and the MV actin binding proteins espin and phosphorylated-ezrin; myosin Id is reduced. Changes in endocytic components include reduced clathrin and adaptin β, and increased disabled-2. Endocytic uptake of lumenal lactoferrin is inhibited in adult, but not neonatal intestinal epithelial cells. There is increased BB membrane-associated expression of both the Na(+)/H(+) exchanger, NHE3 and the Na(+)/phosphate transporter, NaPi2b. These results suggest that Myo6 is involved in the regulated trafficking of NHE3 and NaPi2b between the BB membrane and endosome.
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.
Peter S
PS
Hegan
Hector
H
Giral
Moshe
M
Levi
Mark S
MS
Mooseker
D000818:Animals; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051379:Mice; D008871:Microvilli / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000502:physiology*; D021381:Protein Transport; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000096:biosynthesis
C493558:Slc34a2 protein, mouse; C000613386:Slc9a3 protein, mouse; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; C089785:myosin VI; D018995:Myosin Heavy Chains