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Comparative interactomics analysis reveals potential regulators of ?6?4 distribution in keratinocytes.


ABSTRACT: The integrin ?6?4 and cytoskeletal adaptor plectin are essential components of type I and type II hemidesmosomes (HDs). We recently identified an alternative type II HD adhesion complex that also contains CD151 and the integrin ?3?1. Here, we have taken a BioID proximity labeling approach to define the proximity protein environment for ?6?4 in keratinocytes. We identified 37 proteins that interacted with both ?6 and ?4, while 20 and 78 proteins specifically interacted with the ?6 and ?4 subunits, respectively. Many of the proximity interactors of ?6?4 are components of focal adhesions (FAs) and the cortical microtubule stabilizing complex (CMSC). Though the close association of CMSCs with ?6?4 in HDs was confirmed by immunofluorescence analysis, CMSCs have no role in the assembly of HDs. Analysis of the ?4 interactome in the presence or absence of CD151 revealed that they are strikingly similar; only 11 different interactors were identified. One of these was the integrin ?3?1, which interacted with ?6?4 more strongly in the presence of CD151 than in its absence. These findings indicate that CD151 does not significantly contribute to the interactome of ?6?4, but suggest a role of CD151 in linking ?3?1 and ?6?4 together in tetraspanin adhesion structures.

SUBMITTER: Te Molder L 

PROVIDER: S-EPMC7438003 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Comparative interactomics analysis reveals potential regulators of α6β4 distribution in keratinocytes.

Te Molder Lisa L   Hoekman Liesbeth L   Kreft Maaike M   Bleijerveld Onno O   Sonnenberg Arnoud A  

Biology open 20200813 8


The integrin α6β4 and cytoskeletal adaptor plectin are essential components of type I and type II hemidesmosomes (HDs). We recently identified an alternative type II HD adhesion complex that also contains CD151 and the integrin α3β1. Here, we have taken a BioID proximity labeling approach to define the proximity protein environment for α6β4 in keratinocytes. We identified 37 proteins that interacted with both α6 and β4, while 20 and 78 proteins specifically interacted with the α6 and β4 subunits  ...[more]

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