PMID- 32116023
OWN - NLM
STAT- MEDLINE
DCOM- 20200728
LR  - 20200728
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Linking)
VI  - 318
IP  - 5
DP  - 2020 May 1
TI  - SNX27 regulates DRA activity and mediates its direct recycling by PDZ-interaction 
      in early endosomes at the apical pole of Caco2 cells.
PG  - G854-G869
LID - 10.1152/ajpgi.00374.2019 [doi]
AB  - DRA (downregulated in adenoma, SLC26A3) and NHE3 (Na(+)/H(+) exchanger 3, SLC9A3) 
      together mediate intestinal electroneutral NaCl absorption. Both transporters 
      contain PDZ (postsynaptic density 95, disc large, zonula occludens 1) binding 
      motifs and interact with PDZ adaptor proteins regulating their activity and 
      recycling. SNX27 (sorting nexin 27) contains a PDZ domain and is involved in the 
      recycling of cargo proteins including NHE3. The interaction of SNX27 with DRA and 
      its potential role for the activity and recycling of DRA have been evaluated in 
      this study. SNX27 specifically interacts with DRA via its PDZ domain. The 
      knockdown (KD) of SNX27 reduced DRA activity by 50% but was not accompanied by a 
      decrease of DRA surface expression. This indicates that DRA is trafficked to 
      specific functional domains in the plasma membrane in which DRA is particularly 
      active. Consistently, the disruption of lipid raft integrity by 
      methyl-beta-cyclodextrin has an inhibitory effect on DRA activity that was strongly 
      reduced after SNX27 KD. In differentiated intestinal Caco2 cells, superresolution 
      microscopy and a novel quantitative axial approach revealed that DRA and SNX27 
      colocalize in rab5-positive early endosomes at the apical pole. SNX27 regulates 
      the activity of DRA in the apical plasma membrane through binding with its PDZ 
      domain. This interaction occurs in rab5-positive early endosomes at the apical 
      pole of differentiated intestinal Caco2 cells. SNX27 is involved in the direct 
      recycling of DRA to the plasma membrane where it is inserted into lipid rafts 
      facilitating increased activity.NEW & NOTEWORTHY SNX27 has a PDZ domain and is 
      involved in the regulation and recycling of transmembrane proteins. The role of 
      SNX27 on the activity and recycling of the intestinal Cl(-)/HCO3- exchanger DRA 
      has not yet been studied. This study shows that SNX27 directly interacts with DRA 
      in early endosomes at the apical pole of intestinal Caco2 cells and mediates its 
      direct recycling to facilitate high activity in lipid rafts in the apical plasma 
      membrane.
FAU - Bannert, Karen
AU  - Bannert K
AD  - Department of Gastroenterology and Endocrinology, Center for Internal Medicine, 
      Rostock University Medical Center, Rostock, Germany.
FAU - Berlin, Peggy
AU  - Berlin P
AUID- ORCID: 0000-0001-8354-6970
AD  - Department of Gastroenterology and Endocrinology, Center for Internal Medicine, 
      Rostock University Medical Center, Rostock, Germany.
FAU - Reiner, Johannes
AU  - Reiner J
AD  - Department of Gastroenterology and Endocrinology, Center for Internal Medicine, 
      Rostock University Medical Center, Rostock, Germany.
FAU - Lemcke, Heiko
AU  - Lemcke H
AD  - Department of Cardiac Surgery, Rostock University Medical Center, Rostock, 
      Germany.
AD  - Department Life, Light and Matter, University of Rostock, Rostock, Germany.
FAU - David, Robert
AU  - David R
AD  - Department of Cardiac Surgery, Rostock University Medical Center, Rostock, 
      Germany.
AD  - Department Life, Light and Matter, University of Rostock, Rostock, Germany.
FAU - Engelmann, Robby
AU  - Engelmann R
AD  - Institute of Immunology, Rostock University Medical Center, Rostock, Germany.
FAU - Lamprecht, Georg
AU  - Lamprecht G
AD  - Department of Gastroenterology and Endocrinology, Center for Internal Medicine, 
      Rostock University Medical Center, Rostock, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200302
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Chloride-Bicarbonate Antiporters)
RN  - 0 (SLC26A3 protein, human)
RN  - 0 (SNX27 protein, human)
RN  - 0 (Sorting Nexins)
RN  - 0 (Sulfate Transporters)
RN  - EC 3.6.1.- (RAB5C protein, human)
RN  - EC 3.6.5.2 (rab5 GTP-Binding Proteins)
SB  - IM
MH  - Caco-2 Cells
MH  - *Cell Polarity
MH  - Chloride-Bicarbonate Antiporters/genetics/*metabolism
MH  - Endosomes/*metabolism
MH  - Epithelial Cells/*metabolism
MH  - Humans
MH  - Intestinal Mucosa/*metabolism
MH  - Membrane Microdomains/metabolism
MH  - PDZ Domains
MH  - Protein Binding
MH  - Protein Interaction Domains and Motifs
MH  - Protein Transport
MH  - Sorting Nexins/genetics/*metabolism
MH  - Sulfate Transporters/genetics/*metabolism
MH  - rab5 GTP-Binding Proteins/metabolism
OTO - NOTNLM
OT  - SLC26A3
OT  - SNX27
OT  - anion/chloride transport
OT  - intracellular trafficking
OT  - membrane recycling
OT  - superresolution microscopy
EDAT- 2020/03/03 06:00
MHDA- 2020/07/29 06:00
CRDT- 2020/03/03 06:00
PHST- 2020/03/03 06:00 [pubmed]
PHST- 2020/07/29 06:00 [medline]
PHST- 2020/03/03 06:00 [entrez]
AID - 10.1152/ajpgi.00374.2019 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2020 May 1;318(5):G854-G869. doi: 
      10.1152/ajpgi.00374.2019. Epub 2020 Mar 2.