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