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Vol. 14, Issue 11, 4365-4375, November 2003
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* Gastroenterology Research;
Oncology Research Unit, The Children's Hospital at Westmead, Westmead, NSW Z145, Australia; and
# Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, Australia
Submitted March 24, 2003;
Revised July 20, 2003;
Accepted July 23, 2003
Monitoring Editor: Anthony Bretscher
Microfilaments have been reported to be polarized in a number of cell types based both on function and isoform composition. There is evidence that microfilaments are involved in the movement of vesicles and the polarized delivery of proteins to specialized membrane domains. We have investigated the composition of actin microfilaments in gastrointestinal epithelial cells and their role in the delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) into the apical membrane using cultured T84 cells as a model. We identified a specific population of microfilaments containing the tropomyosin (Tm) isoforms Tm5a and/or Tm5b, which are polarized in T84 cell monolayers. Polarization of this microfilament population occurs very rapidly in response to cell-cell and cell-substratum contact and is not inhibited by jasplakinolide, suggesting this involves the movement of intact filaments. Colocalization of Tm5a and/or Tm5b and CFTR was observed in long-term cultures. A reduction in Tm5a and Tm5b expression, induced using antisense oligonucleotides, resulted in an increase in both CFTR surface expression and chloride efflux in response to cAMP stimulation. We conclude that Tm isoforms Tm5a and/or Tm5b mark an apical population of microfilaments that can regulate the insertion and/or retention of CFTR into the plasma membrane.
Corresponding author. E-mail address: peterG3{at}chw.edu.au. This article has been cited by other articles:
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  P. Gunning, G. O'neill, and E. Hardeman Tropomyosin-Based Regulation of the Actin Cytoskeleton in Time and Space Physiol Rev, January 1, 2008; 88(1): 1 - 35. [Abstract] [Full Text] [PDF]
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 A. Nazli, A. Wang, O. Steen, D. Prescott, J. Lu, M. H. Perdue, J. D. Soderholm, P. M. Sherman, and D. M. McKay Enterocyte Cytoskeleton Changes Are Crucial for Enhanced Translocation of Nonpathogenic Escherichia coli across Metabolically Stressed Gut Epithelia Infect. Immun., January 1, 2006; 74(1): 192 - 201. [Abstract] [Full Text] [PDF]
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 B. Vrhovski, K. McKay, G. Schevzov, P. W. Gunning, and R. P. Weinberger Smooth Muscle-specific {alpha} Tropomyosin Is a Marker of Fully Differentiated Smooth Muscle in Lung J. Histochem. Cytochem., July 1, 2005; 53(7): 875 - 883. [Abstract] [Full Text] [PDF]
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G. Schevzov, B. Vrhovski, N. S. Bryce, S. Elmir, M. R. Qiu, G. M. O'Neill, N. Yang, N. M. Verrills, M. Kavallaris, and P. W. Gunning Tissue-specific Tropomyosin Isoform Composition J. Histochem. Cytochem., May 1, 2005; 53(5): 557 - 570. [Abstract] [Full Text] [PDF]
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 A. J. Kee, G. Schevzov, V. Nair-Shalliker, C. S. Robinson, B. Vrhovski, M. Ghoddusi, M. R. Qiu, J. J.-C. Lin, R. Weinberger, P. W. Gunning, et al. Sorting of a nonmuscle tropomyosin to a novel cytoskeletal compartment in skeletal muscle results in muscular dystrophy J. Cell Biol., August 30, 2004; 166(5): 685 - 696. [Abstract] [Full Text] [PDF]
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