Title: The%20UNC-112%20gene%20in%20Caenorhabditis%20elegans%20Encodes%20a%20Novel%20Component%20of%20Cell-Matrix%20Adhesion%20Structures%20Required%20for%20Integrin%20Localization%20in%20the%20Muscle%20Cell%20Membrane
1The 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, 150253-264
2The 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
3Muscle
in C. elegans
4Dense Bodies
in C. elegans
This paper focuses on s
interactions with perlecan, vinculin, and
ß-integrin
UNC-112
5UNC-112
and its neighbors
Perlecan located in the basement membrane
Vinculin binds actin a-actinin ß-integrin
major structural TM component
6Dense Bodies
Why are
important?
Muscle fibers need anchors .. in order
to contract!
7Dense Bodies
in C. elegans
8Muscle Assembly during Development
nearly continuous sheet
forms focal adhesions
..the sheet seperates
into muscle quadrants
9UNC-112
Is
a good neighbor?
Perlecan ---gt
lt--- ß-integrin
lt-- FA
Vinculin ---gt
10UNC-112
and UNC-52 / perlecan
wild type (at 3-fold)
unc-112(st581) (PAT)
Adhesion Structures
11UNC-112
and DEB-1 / vinculin
unc-112(st581) (PAT)
wild type (at 3-fold)
Adhesion Structures
12UNC-112
and PAT-3 / ß-integrin
unc-112(st581) (PAT)
wild type (at 3-fold)
Adhesion Structures
13UNC-112
and PAT-3 / ß-integrin
UNC-112GFP colocalizes with PAT-3
immunofluorescence
14UNC-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.
15UNC-112
in wild type embryo
close-up of UNC-112GFP
Myosin light-chain mAb
UNC-112GFP
16UNC-112
in unc-44(-) / deb-1(-)
(vinculin mutant)
close-up of UNC-112GFP
Myosin light-chain mAb
UNC-112GFP
17UNC-112
in unc-52(-) embryo
(perlecan mutant)
close-up of UNC-112GFP
Myosin light-chain mAb
UNC-112GFP
18UNC-112
in pat-3(-) embryo
(ß-integrin mutant)
close-up of UNC-112GFP
Myosin light-chain mAb
UNC-112GFP
19UNC-112
needs a little help..
- Requires ß-integrin perlecan for activation
- Without them, cannot anchor FA complexes
- Myosin is hopelessly lost without UNC-112
20UNC-112
Human Ortholog of
(kindlin-1)
also plays a role in proper attachment of
actin to vinculin
21UNC-112
Human Ortholog of
(kindlin-1)
Otherwise
22UNC-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