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The C-terminus of the transmembrane mucin MUC17 binds to the scaffold protein PDZK1 that stably localizes it to the enterocyte apical membrane in the small intestine

Författare och institution:
Emily Malmberg (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi); Thaher Pelaseyed (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi); Åsa Petersson (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi); Ursula E. Seidler (-); Hugo de Jonge (-); John R. Riordan (-); Gunnar C. Hansson (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi)
Publicerad i:
Biochemical Journal, 410 s. 283-289
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
The membrane bound mucins have a heavily O-glycosylated extracellular domain, a single pass membrane domain and a short cytoplasmic tail. Three of the membrane bound mucins, MUC3, MUC12 and MUC17, are clustered on chromosome 7 and found in the gastrointestinal tract. These mucins have C-terminal sequences typical for PDZ domain binding proteins. To identify PDZ proteins able to interact with the mucins, we screened PDZ domain arrays using YFP-tagged proteins. MUC17 exhibited a strong binding to PDZK1 whereas the binding to NHERF1 was weak. Furthermore, we showed weak binding of MUC12 to PDZK1, NHERF1 and NHERF2. GST pull-down experiments confirmed that the C-terminal tail of MUC17 co-precipitates with the scaffold protein PDZK1 as identified by mass spectrometry. This was mediated through the C-terminal PDZ-interaction site in MUC17 which was capable of binding to three of the four PDZ domains in PDZK1. Immunostaining of wild-type or Pdzk1-/- mouse jejunum with an antiserum against Muc3(17), the mouse orthologue of human MUC17, revealed strong brush border membrane staining in the wild-type mice compared to an intracellular Muc3(17) staining in the Pdzk1-/- mice. This suggests that Pdzk1 plays a specific role in stabilizing Muc3(17) in the apical membrane of small intestinal enterocytes.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
cystic fibrosis transmembrane conductance regulator (CFTR), Muc3, MS, Na+/H+-exchanger regulatory factor 1, (NHERF1), PDZ domain protein, transmembrane mucin
Postens nummer:
Posten skapad:
2008-01-10 15:09
Posten ändrad:
2012-03-26 14:07

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