CSB327 Lecture 12 Summary

5 Pages
147 Views
Unlock Document

Department
Cell and Systems Biology
Course
CSB327H1
Professor
Maurice Ringuette
Semester
Fall

Description
Lecture 12 Syndecan-4 - A family of transmembrane proteoglycans - The major of cell surface heparin sulfates - Structure o Ectodomain (N-terminus)  HS-GAGs are low affinity co-receptors  HS-GAGs bind to FN to activate intracellular signalling events that stabilize FA  HS-GAGs bind to several growth factors to present them to their cognate receptors  HS-GAGs bind to and present FGF to their cognate FGFR on the same cell  CS-GAGs o Single-span TM domain o Short endodomain (C-terminus)  C1  Ser183  Associates with actin cytoskeleton  V  Lysine rich domain  PIP2 binding domain  PKCα binding domain  Syndesmos binding domain  C2  PDZ binding domain (e.g., syntenin) - PI3K generates PI docking sites o PI  PIP  PIP2  PLC breaks down PIP2 into diacylglycerol and IP3 o PI3K adds phosphate PIP  PIP2 o PI3K adds phosphate PIP2  PIP3 o PIP2 and PIP3 serve as docking sites for proteins with PH domains o Both forms of PIP2 serve as docking sites for proteins with PH domains o PTEN dephosphorylate PIP2 and PIP3  Cancer cells have mutated PTEN - Regulation of focal adhesion turnover by syndecan-4 o Syndecan-4 underexpression forms smaller FA and decrease cell motility o Syndecan-4 overexpression forms larger FA and decrease cell motility o Syndecan-4 maintains an intermediate state of adhesion to promote cell migration - Mechanism o Binding of FN to α5β1 integrin increase the level of PIP2  Binding of FN to α4β1 is syndecan independent o PIP2 binds to the V domain of syndecan-4 o PIP2 promotes the oligomerization of syndecan-4 o PIP2-syndecan-4 complex recruits and superactivates PKCα by autophosphorylation o Clustering of syndecan-4 and PKCα recruits syndesmos to the PM o Syndesmos interaction with paxillin stabilizes FA o Syndesmos and paxillin are phosphorylated PKCα o FN binding to integrin  increase PIP2  PIP2 binds to syndecan-4  syndecan-4 oligomerization  superactivates PKCα  recruits syndesmos to PM  syndesmos binds to paxillin  promotes FA stability - Turnover o HS-GAGs are co-receptors for bFGF-2 o HS-GAGs presents bGFG-2 to bFGFR-2 on the same cell o HS-GAGS activate bFGFR-2 signalling o bFGFR-2 signaling recruits and activates PKCδ to the PM o PKCδ phosphorylates Ser183 on syndecan-4 in C1 domain o p-Ser183 inhibits the affinity of syndecan-4 for PIP2 o p-Ser183 inhibits syndecan-4 oligomerization o p-Ser183 inhibits PKCα superactivation o p-Ser183 promotes FA turnover o bFGF-2  recruits PKCδ to PM  phosphorylates Ser183  inhibits syndecan-4 oligomerization  promotes focal adhesion turnover o bFGFR-2 signaling activates Ser/Thr phosphatase 1/2A o Ser/Thr phosphatase 1/2A dephosphorylates Ser183 on syndecan-4 o Ser183 promotes syndecan-4 oligomerization  promotes FA formation o bFGF-2  activates phosphatase 1/2A  dephosphorylates Ser183  promotes syndecan-4 oligomerization  promotes FA formation - Integrin-mediated FA formation is dependent on syndecan-4 o Cell binding domain of FN  Cells attach and spread  No FA formation o Cell binding domain of FN + Activating Ab against syndecan-4  FA formation  Activating Ab is substituting for the absence of the heparin binding domain of FN o Cell binding domain of FN + Heparin binding domain of FN  FA formation o Absence of syndecan-4  Cells attach an spread  No FA formation o Absence of PKCα  No FA formation Integrins - Heterodimeric transmembrane receptors composed of non-covalently associated α and β subunits (e.g., 24 distinct heterodimers) o β1 subfamily can associate with 12 α subunits  inactivation of the β1 chain results in early embryonic death o β2 subfamily can associate with I-CAMs o αv subfamily restricted to WBCs - No intrinsic enzymatic activity o Inte
More Less

Related notes for CSB327H1

Log In


OR

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


OR

By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.


Submit