the unc-112 gene in caenorhabditis elegans encodes a novel component of cell-matrix adhesion...
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, 150:253-264
Benjamin D. WilliamsAssociate Professor of Cell & Structural BiologyUniversity of Illinois
Sc.B., Brown University (Biology)Ph.D., Yale University (Biology)Postdoc., Washington University School of Medicine
Donald G. MoermanProfessor
B.Sc,, Ph.D., Simon FraserPostdoc, Washington University School of MedicineVisiting Scientist, Max-Planck Institute for Biochemistry
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Teresa RogalskiResearch ScientistDepartment of Zoology
Ph.D., Simon Fraser
Gregory MullenDepartment of ZoologyUBC
Mary GilbertDepartment of ZoologyUBC
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This paper focuses on `s interactions with perlecan, vinculin, and ß-integrin
Perlecan: located in the basement membrane Vinculin: binds actin & a-actininß-integrin: major structural TM component
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Muscle
fibers
need
anchors
…….. in order
to
contract!
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nearly continuous sheet
forms focal adhesions
..the sheet seperates
into muscle quadrants
Perlecan --->Perlecan --->
Vinculin ---Vinculin --->>
<--- ß-integrin<--- ß-integrin
IsIs a good neighbor?a good neighbor?
<-- <-- FAFA
wild type(at 3-fold)
unc-112(st581) (PAT)
AdhesionStructures
unc-112(st581) (PAT)
AdhesionStructures
wild type(at 3-fold)
unc-112(st581) (PAT)
AdhesionStructures
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 mAb UNC-112::GFP close-up of
UNC-112::GFP
Myosin light-chain mAb UNC-112::GFP close-up of
UNC-112::GFP
(vinculin mutant)
Myosin light-chain mAb UNC-112::GFP close-up of
UNC-112::GFP
(perlecan mutant)
Myosin light-chain mAb UNC-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
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Human Ortholog of (kindlin-1)
…also plays a role in
proper attachment
of actin to
vinculin
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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