Journal
TRAFFIC
Volume 8, Issue 8, Pages 998-1006Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1600-0854.2007.00587.x
Keywords
CFTR; diarrhea; endocytosis; intestine; myosin VI; Snell's Waltzer mice
Categories
Funding
- NIDDK NIH HHS [DK1K08DK02846, R37DK54425, 1R03DK073486-01] Funding Source: Medline
Ask authors/readers for more resources
In polarized epithelial cells such as those that line the inner ear, kidney and gut, myosin VI has been localized to the intermicrovillar domains where it is proposed to regulate clathrin-dependent endocytosis; however, a direct role for myosin VI in apical endocytosis has not been shown. We examined the apical membrane distribution and endocytosis of cystic fibrosis transmembrane conductance regulator (CFTR) in myosin VI-deficient Snell's Waltzer Myo6((sv/sv)) mice. Confocal microscopy and cell-surface biotinylation confirmed that surface levels of CFTR in the intestine of Myo6((sv/sv))) mice were markedly higher, and CFTR internalization from the apical plasma membrane was reduced compared with heterozygous controls. Consistent with a defect in CFTR endocytosis and accumulation at the cell surface, exaggerated CFTR-mediated fluid secretion was observed in Myo6((sv/sv)) mice following treatment of isolated jejunum with the cyclic GMP-activated heat stable enterotoxin. These data establish that myosin VI modulates apical endocytosis and may be an important physiological modulator of CFTR function and CFTR-associated secretory diarrhea in the gut.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available