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The UNC-112 gene in Caenorhabditis elegans Encodes a Novel Component of Cell-Matrix Adhesion Structures Required for Integrin Localization in the Muscle Cell Membrane. Rogalski T.M., Mullen G.P., Gilbert M.M., Williams B.D., and D.G. Moerman Journal of Cell Biology, 150:253-264. The Authors.
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The UNC-112 gene in Caenorhabditis elegans Encodes a Novel Component of Cell-Matrix Adhesion Structures Required for Integrin Localization in the Muscle Cell Membrane Rogalski T.M., Mullen G.P., Gilbert M.M., Williams B.D., and D.G. Moerman Journal of Cell Biology, 150:253-264
The Authors Teresa Rogalski Research Scientist Department of Zoology Ph.D., Simon Fraser Gregory Mullen Department of Zoology UBC Mary Gilbert Department of Zoology UBC Donald G. Moerman Professor B.Sc,, Ph.D., Simon Fraser Postdoc, Washington University School of Medicine Visiting Scientist, Max-Planck Institute for Biochemistry Benjamin D. Williams Associate Professor of Cell & Structural Biology University of Illinois Sc.B., Brown University (Biology) Ph.D., Yale University (Biology) Postdoc., Washington University School of Medicine
Muscle in C. elegans
Dense Bodies in C. elegans This paper focuses on `s interactions with perlecan, vinculin, and ß-integrin UNC-112
UNC-112 and its neighbors Perlecan: located in the basement membrane Vinculin: binds actin & a-actinin ß-integrin: major structural TM component
Dense Bodies Why are important? Muscle fibers need anchors …….. in order to contract!
Dense Bodies in C. elegans
Muscle Assembly during Development nearly continuous sheet forms focal adhesions ..the sheet seperates into muscle quadrants
UNC-112 Is a good neighbor? Perlecan ---> <--- ß-integrin <-- FA Vinculin --->
UNC-112 and UNC-52 / perlecan wild type (at 3-fold) unc-112(st581) (PAT) Adhesion Structures
UNC-112 and DEB-1 / vinculin wild type (at 3-fold) unc-112(st581) (PAT) Adhesion Structures
UNC-112 and PAT-3 / ß-integrin wild type (at 3-fold) unc-112(st581) (PAT) Adhesion Structures
UNC-112 and PAT-3 / ß-integrin UNC-112::GFP colocalizes with PAT-3 immunofluorescence
UNC-112 lends a hand.. • Required for proper ß-integrin localization • Is needed to organize vinculin & perlecan* • However, vinculin does not need UNC-112 to localize itself with ß-integrin *but not required.
UNC-112 in wild type embryo close-up of UNC-112::GFP Myosin light-chain mAb UNC-112::GFP
UNC-112 in unc-44(-) / deb-1(-) (vinculin mutant) close-up of UNC-112::GFP Myosin light-chain mAb UNC-112::GFP
UNC-112 in unc-52(-) embryo (perlecan mutant) close-up of UNC-112::GFP Myosin light-chain mAb UNC-112::GFP
UNC-112 in pat-3(-) embryo (ß-integrin mutant) close-up of UNC-112::GFP Myosin light-chain mAb UNC-112::GFP
UNC-112 needs a little help.. • Requires ß-integrin & perlecan for activation • Without them, cannot anchor FA complexes • Myosin is hopelessly lost without UNC-112
UNC-112 Human Ortholog of (kindlin-1) …also plays a role in proper attachment of actin to vinculin
UNC-112 Human Ortholog of (kindlin-1) Otherwise……
UNC-112 Summary • Not required for: • -- Polarization of muscle cell membrane • -- Focal Adhesion (FA) complex formation • Required for: • - Neat and orderly arrays of FA complexes • -- Proper attachment of actin to FAs • - Any Attachment of Myosin to FAs