TY - JOUR
T1 - Plakophilin 3 and Par3 facilitate desmosomes' association with the apical junctional complex
AU - Indra, Indrajyoti
AU - Troyanovsky, Regina B.
AU - Green, Kathleen J.
AU - Troyanovsky, Sergey M.
N1 - Funding Information:
Sequencing, flow cytometry, and confocal microscopy were performed at the Northwestern University Genetic, Flow Cytometry, and Advanced Microscopy Centers. The authors declare no competing financial interests. The work was supported by grants from the National Institutes of Health: AR44016 and AR070166 (to S.M.T.), and R37AR043380 and R01AR041836 (to K.J.G.).
Publisher Copyright:
© 2021 Indra et al.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Desmosomes (DSMs), together with adherens junctions (AJs) and tight junctions (TJs), constitute the apical cell junctional complex (AJC). While the importance of the apical and basolateral polarity machinery in the organization of AJs and TJs is well established, how DSMs are positioned within the AJC is not understood. Here we use highly polarized DLD1 cells as a model to address how DSMs integrate into the AJC. We found that knockout (KO) of the desmosomal ARM protein Pkp3, but not other major DSM proteins, uncouples DSMs from the AJC without blocking DSM assembly. DLD1 cells also exhibit a prominent extraDSM pool of Pkp3, concentrated in tricellular (tC) contacts. Probing distinct apicobasal polarity pathways revealed that neither the DSM's association with AJC nor the extraDSM pool of Pkp3 are abolished in cells with defects in Scrib module proteins responsible for basolateral membrane development. However, a loss of the apical polarity protein, Par3, completely eliminates the extraDSM pool of Pkp3 and disrupts AJC localization of desmosomes, dispersing these junctions along the entire length of cell-cell contacts. Our data are consistent with a model whereby Par3 facilitates DSM assembly within the AJC, controlling the availability of an assembly competent pool of Pkp3 stored in tC contacts.
AB - Desmosomes (DSMs), together with adherens junctions (AJs) and tight junctions (TJs), constitute the apical cell junctional complex (AJC). While the importance of the apical and basolateral polarity machinery in the organization of AJs and TJs is well established, how DSMs are positioned within the AJC is not understood. Here we use highly polarized DLD1 cells as a model to address how DSMs integrate into the AJC. We found that knockout (KO) of the desmosomal ARM protein Pkp3, but not other major DSM proteins, uncouples DSMs from the AJC without blocking DSM assembly. DLD1 cells also exhibit a prominent extraDSM pool of Pkp3, concentrated in tricellular (tC) contacts. Probing distinct apicobasal polarity pathways revealed that neither the DSM's association with AJC nor the extraDSM pool of Pkp3 are abolished in cells with defects in Scrib module proteins responsible for basolateral membrane development. However, a loss of the apical polarity protein, Par3, completely eliminates the extraDSM pool of Pkp3 and disrupts AJC localization of desmosomes, dispersing these junctions along the entire length of cell-cell contacts. Our data are consistent with a model whereby Par3 facilitates DSM assembly within the AJC, controlling the availability of an assembly competent pool of Pkp3 stored in tC contacts.
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U2 - 10.1091/mbc.E21-01-0001
DO - 10.1091/mbc.E21-01-0001
M3 - Article
C2 - 34260281
AN - SCOPUS:85114487709
VL - 32
SP - 1824
EP - 1837
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 19
ER -