The UNC-112 gene in Caenorhabditis elegans Encodes a Novel Component of Cell-Matrix Adhesion Structures Required for Integrin Localization in the Muscle.

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Presentation transcript:

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:

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 Donald G. Moerman Professor B.Sc,, Ph.D., Simon Fraser Postdoc, Washington University School of Medicine Visiting Scientist, Max-Planck Institute for Biochemistry Teresa Rogalski Research Scientist Department of Zoology Ph.D., Simon Fraser Gregory Mullen Department of Zoology UBC Mary Gilbert Department of Zoology UBC

This paper focuses on `s interactions with perlecan, vinculin, and ß-integrin

Perlecan: located in the basement membrane Vinculin: binds actin & a-actinin ß-integrin: major structural TM component

Muscle fibers need anchors …….. in order to contract!

nearly continuous sheet forms focal adhesions..the sheet seperates into muscle quadrants

Perlecan ---> Vinculin ---> <--- ß-integrin Is a good neighbor? a good neighbor? <-- FA

wild type (at 3-fold) unc-112(st581) (PAT) Adhesion Structures

unc-112(st581) (PAT) Adhesion Structures wild type (at 3-fold)

unc-112(st581) (PAT) Adhesion Structures wild type (at 3-fold)

UNC-112::GFP colocalizes with PAT-3 immunofluorescence

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.

Myosin light-chain mAbUNC-112::GFP close-up of UNC-112::GFP

Myosin light-chain mAbUNC-112::GFP close-up of UNC-112::GFP (vinculin mutant)

Myosin light-chain mAbUNC-112::GFP close-up of UNC-112::GFP (perlecan mutant)

Myosin light-chain mAbUNC-112::GFP close-up of UNC-112::GFP (ß-integrin mutant)

Requires ß-integrin & perlecan for activation Without them, cannot anchor FA complexes Myosin is hopelessly lost without UNC-112

Human Ortholog of(kindlin-1) …also plays a role in proper attachment of actin to vinculin

Human Ortholog of(kindlin-1) Otherwise……

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