Dynamic microtubules regulate the local concentration of E-cadherin at cell-cell contacts.
In contrast to the well-established relationship between cadherins and the actin cytoskeleton, the potential link between cadherins and microtubules (MTs) has been less extensively investigated. We now identify a pool of MTs that extend radially into cell-cell contacts and are inhibited by manoeuvres that block the dynamic activity of MT plus-ends (e.g. in the presence of low concentrations of nocodazole and following expression of a CLIP-170 mutant). Blocking dynamic MTs perturbed the ability of cells to concentrate and accumulate E-cadherin at cell-cell contacts, as assessed both by quantitative immunofluorescence microscopy and fluorescence recovery after photobleaching (FRAP) analysis, but did not affect either transport of E-cadherin to the plasma membrane or the amount of E-cadherin expressed at the cell surface. This indicated that dynamic MTs allow cells to concentrate E-cadherin at cell-cell contacts by regulating the regional distribution of E-cadherin once it reaches the cell surface. Importantly, dynamic MTs were necessary for myosin II to accumulate and be activated at cadherin adhesive contacts, a mechanism that supports the focal accumulation of E-cadherin. We propose that this population of MTs represents a novel form of cadherin-MT cooperation, where cadherin adhesions recruit dynamic MTs that, in turn, support the local concentration of cadherin molecules by regulating myosin II activity at cell-cell contacts.
Stehbens
Samantha J
SJ
Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
Paterson
Andrew D
AD
Crampton
Matthew S
MS
Shewan
Annette M
AM
Ferguson
Charles
C
Akhmanova
Anna
A
Parton
Robert G
RG
Yap
Alpha S
AS
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D016466:CHO Cells; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D024462:Myosin Type II / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D015739:Nocodazole / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D015820:Cadherins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; C076744:cytoplasmic linker protein 170; D024462:Myosin Type II; D015739:Nocodazole