Transcript The UNC-112 gene in Caenorhabditis elegans Encodes a Novel

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
Teresa Rogalski
Research Scientist
Department of Zoology
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Ph.D., Simon Fraser
Gregory Mullen
Department of Zoology
UBC
Mary Gilbert
Department of Zoology
UBC
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
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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-actinin
ß-integrin: major structural TM component
Muscle
fibers
need
anchors
…….. in
order
to
contract!
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nearly continuous sheet
forms focal adhesions
..the sheet seperates
into muscle quadrants
Is
a good neighbor?
Perlecan --->
<--- ß-integrin
<-- FA
Vinculin --->
wild type
(at 3-fold)
unc-112(st581)
(PAT)
Adhesion
Structures
wild type
(at 3-fold)
unc-112(st581)
(PAT)
Adhesion
Structures
wild type
(at 3-fold)
unc-112(st581)
(PAT)
Adhesion
Structures
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
(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)
Myosin light-chain mAb
UNC-112::GFP
close-up of
UNC-112::GFP
• 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
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vinculin
Human Ortholog of
(kindlin-1)
Otherwise……
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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