PMID- 33596089
OWN - NLM
STAT- MEDLINE
DCOM- 20210914
LR  - 20221013
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 32
IP  - 8
DP  - 2021 Apr 15
TI  - Regulation of intestinal epithelial intercellular adhesion and barrier function 
      by desmosomal cadherin desmocollin-2.
PG  - 753-768
LID - 10.1091/mbc.E20-12-0775 [doi]
AB  - The role of desmosomal cadherin desmocollin-2 (Dsc2) in regulating barrier 
      function in intestinal epithelial cells (IECs) is not well understood. Here, we 
      report the consequences of silencing Dsc2 on IEC barrier function in vivo using 
      mice with inducible intestinal-epithelial-specific Dsc2 knockdown (KD) 
      (Dsc2(ERDeltaIEC)). While the small intestinal gross architecture was maintained, 
      loss of epithelial Dsc2 influenced desmosomal plaque structure, which was smaller 
      in size and had increased intermembrane space between adjacent epithelial cells. 
      Functional analysis revealed that loss of Dsc2 increased intestinal permeability 
      in vivo, supporting a role for Dsc2 in the regulation of intestinal epithelial 
      barrier function. These results were corroborated in model human IECs in which 
      Dsc2 KD resulted in decreased cell-cell adhesion and impaired barrier function. 
      It is noteworthy that Dsc2 KD cells exhibited delayed recruitment of desmoglein-2 
      (Dsg2) to the plasma membrane after calcium switch-induced intercellular junction 
      reassembly, while E-cadherin accumulation was unaffected. Mechanistically, loss 
      of Dsc2 increased desmoplakin (DP I/II) protein expression and promoted 
      intermediate filament interaction with DP I/II and was associated with enhanced 
      tension on desmosomes as measured by a Dsg2-tension sensor. In conclusion, we 
      provide new insights on Dsc2 regulation of mechanical tension, adhesion, and 
      barrier function in IECs.
FAU - Raya-Sandino, Arturo
AU  - Raya-Sandino A
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 
      48109.
FAU - Luissint, Anny-Claude
AU  - Luissint AC
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 
      48109.
FAU - Kusters, Dennis H M
AU  - Kusters DHM
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 
      48109.
FAU - Narayanan, Vani
AU  - Narayanan V
AD  - Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, 
      VA 23284.
FAU - Flemming, Sven
AU  - Flemming S
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 
      48109.
FAU - Garcia-Hernandez, Vicky
AU  - Garcia-Hernandez V
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 
      48109.
FAU - Godsel, Lisa M
AU  - Godsel LM
AD  - Departments of Pathology and Dermatology, Feinberg School of Medicine, 
      Northwestern University, Chicago, IL 60611.
FAU - Green, Kathleen J
AU  - Green KJ
AD  - Departments of Pathology and Dermatology, Feinberg School of Medicine, 
      Northwestern University, Chicago, IL 60611.
AD  - Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, 
      IL 60611.
FAU - Hagen, Susan J
AU  - Hagen SJ
AD  - Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02115.
FAU - Conway, Daniel E
AU  - Conway DE
AD  - Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, 
      VA 23284.
FAU - Parkos, Charles A
AU  - Parkos CA
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 
      48109.
FAU - Nusrat, Asma
AU  - Nusrat A
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 
      48109.
LA  - eng
GR  - R01 DK079392/DK/NIDDK NIH HHS/United States
GR  - R37 AR043380/AR/NIAMS NIH HHS/United States
GR  - R29 DK055679/DK/NIDDK NIH HHS/United States
GR  - T32 CA009560/CA/NCI NIH HHS/United States
GR  - R01 AR043380/AR/NIAMS NIH HHS/United States
GR  - R03 AR068096/AR/NIAMS NIH HHS/United States
GR  - R01 DK072564/DK/NIDDK NIH HHS/United States
GR  - P30 DK034854/DK/NIDDK NIH HHS/United States
GR  - R56 DK089763/DK/NIDDK NIH HHS/United States
GR  - P30 DK034933/DK/NIDDK NIH HHS/United States
GR  - R35 GM119617/GM/NIGMS NIH HHS/United States
GR  - R01 DK055679/DK/NIDDK NIH HHS/United States
GR  - R01 AR041836/AR/NIAMS NIH HHS/United States
GR  - R01 DK089763/DK/NIDDK NIH HHS/United States
GR  - R01 DK059888/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210217
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Cadherins)
RN  - 0 (DSC2 protein, human)
RN  - 0 (Desmocollins)
RN  - 0 (Desmoglein 2)
RN  - 0 (Desmosomal Cadherins)
RN  - 0 (Dsc2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cadherins/metabolism
MH  - Cell Adhesion/*physiology
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Desmocollins/genetics/*metabolism/physiology
MH  - Desmoglein 2/metabolism
MH  - Desmosomal Cadherins/metabolism/physiology
MH  - Desmosomes/metabolism
MH  - Humans
MH  - Intercellular Junctions/metabolism
MH  - Intestinal Mucosa
MH  - Male
MH  - Mice
MH  - Mice, Knockout
PMC - PMC8108520
EDAT- 2021/02/18 06:00
MHDA- 2021/09/15 06:00
PMCR- 2021/06/30
CRDT- 2021/02/17 17:08
PHST- 2021/02/18 06:00 [pubmed]
PHST- 2021/09/15 06:00 [medline]
PHST- 2021/02/17 17:08 [entrez]
PHST- 2021/06/30 00:00 [pmc-release]
AID - E20-12-0775 [pii]
AID - 10.1091/mbc.E20-12-0775 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2021 Apr 15;32(8):753-768. doi: 10.1091/mbc.E20-12-0775. Epub 2021 
      Feb 17.