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Molecular Genetics and Cell Biology


Research Projects:

Septate Junctions

 
 

 

A central problem in the development and function of epithelial cells is the process by which specialized membrane domains are formed and maintained. These domains, including the apical and basolateral membranes, the junctional complex, and other subdomains, are important in organizing and compartmentalizing membrane-related functions. Intercellular junctions, including adherens, tight, and septate junctions, have well-defined structural functions in intercellular adhesion and preventing paracellular flow. In addition, there is an increasing body of evidence that these junctions, and other specialized membrane domains, play an essential role in regulating signaling pathways.

The overall goal of this project is to better understand the functions of the epithelial septate junction, a key part of the junctional complex that forms between Drosophila epithelial cells. Septate junctions are structurally and molecularly homologous to the mammalian paranodal junction that separates the node of Ranvier from the myelinated portion of the axon. Thus studies of the insect septate junction are directly relevant to understanding axon-glial interactions in the mammalian nervous system. Studies in our laboratory and others have identified a handful of septate junction components, but we still have a very limited understanding of either its structure or function. Current studies in the laboratory seek to

1) identify new septate junction components through genetic and genomic screens,

2) clarify functional relationships between the septate junction and apical/basal epithelial polarity, and

3) understand the role of these junctions in growth control.

 


Optical section of a fold in the wing imaginal epithelium stained with anti-Moesin (red: apical membrane), anti-Ecadherin (blue: adherens junctions), and anti-Coracle (green: septate junction).
Closely apposed apical surfaces in the fold give the appearance of a single line of Moesin staining, flanked on either side by adjacent adherens and septate junctions more basally.

 

 

Related publications:

Fehon RG, Dawson IA, Artavanis-Tsakonas S. A Drosophila homologue of membrane-skeleton protein 4.1 is associated with septate junctions and is encoded by the coracle gene. Development. 1994 Mar;120(3):545-57. (PubMed)

Ward RE 4th, Lamb RS, Fehon RG. A conserved functional domain of Drosophila coracle is required for localization at the septate junction and has membrane-organizing activity. J Cell Biol. 1998 Mar 23;140(6):1463-73. (PubMed)

Lamb RS, Ward RE, Schweizer L, Fehon RG. Drosophila coracle, a member of the protein 4.1 superfamily, has essential structural functions in the septate junctions and developmental functions in embryonic and adult epithelial cells. Mol Biol Cell. 1998 Dec;9(12):3505-19. (PubMed)

Tepass U, Tanentzapf G, Ward R, Fehon R. Epithelial cell polarity and cell junctions in Drosophila. Annu Rev Genet. 2001;35:747-84. Review. (PubMed)

Ward RE 4th, Schweizer L, Lamb RS, Fehon RG. The protein 4.1, ezrin, radixin, moesin (FERM) domain of Drosophila Coracle, a cytoplasmic component of the septate junction, provides functions essential for embryonic development and imaginal cell proliferation. Genetics. 2001 Sep;159(1):219-28. (PubMed)

Genova JL, Fehon RG. Neuroglian, Gliotactin, and the Na+/K+ ATPase are essential for septate junction function in Drosophila. J Cell Biol. 2003 Jun 9;161(5):979-89. Epub 2003 Jun 2. (PubMed)

Nilton, A., Oshima, K., Zare, F., Byri, S., Nannmark, U., Nyberg, K.G., Fehon, R.G., and Uv, A.E. Crooked, Coiled and Crimpled are three Ly6-like proteins required for proper localization of septate junction components. Development. 2010 137: 2427-37. (PubMed)

Oshima, K. and Fehon, R.G. Analysis of protein dynamics within the septate junction reveals a highly stable core protein complex that does not include the basolateral polarity protein Discs Large. J. Cell Sci. 2011 124: 2861-71. (PubMed)

Hall, S., Bone, C., Oshima, K., Zhang, L., McGraw, M., Lucas, B., Fehon, R.G., and Ward, R.E. Macroglobulin complement-related encodes a protein required for septate junction organization and paracellular barrier function in Drosophila. Development. 2014 141: 889-898. (PubMed)

 

 

Fehon Lab Research Projects:

Tissue Growth Control  
Epithelial Integrity  

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