PgmNr W4044: Asymmetric positioning of organelles during epithelial cell polarization.

Authors:
James Brandt; Greg Hermann


Institutes
Lewis & Clark College, Portland, OR.


Keyword: Cell asymmetry

Abstract:

The intestinal cells of C. elegans display asymmetrical positioning of multiple organelles soon after they become polarized at the E16 stage. At this point in intestinal development, early and late endosomes, nuclei, and lysosomes are positioned near the nascent apical membrane while yolk granules are positioned basally. Our group studies the formation and behavior of an intestinal cell-specific lysosome related organelle (LRO) called the gut granule. The asymmetric positioning of LROs can be essential for their function, for example in movement of lytic granules to the immunological synapse in cytotoxic T-cells. In wild-type embryos, gut granules are positioned basally and excluded from the apical domain, which is where the nucleus is located. In unc-83(-) mutants, which lack polarized nuclei, gut granules are located both apically and basally, indicating that the positioning of the nucleus excludes gut granules from the apical domain. We have found that defects in two genes encoding ATP binding cassette (ABC) transporters lead to the accumulation of gut granules near the apical membrane. In these mutants, nuclei are still positioned apically. It is possible that gut granules are mispolarized in the mutants due to taking on the identity of an apical organelle. Our colocalization analyses between gut granule markers and markers for apically polarized organelles, including early endosomes (RAB-5, FYVE::GFP), late endosomes (RAB-7), and lysosomes (LMP-1), suggest the identity of gut granules are unaltered in the mutants. The positioning of endolysosomes, nuclei, and yolk were not altered in the mutants indicating that the overall cytoplasmic polarity of intestinal cells is not reversed. Interestingly, mutations in mrp-4, another ABC transporter, suppress the asymmetrical polarization of gut granules in the mutants. We will present models for the function of these ABC transporters in gut granule positioning.



Wormbase Genetic Index
1. unc-83
2. mrp-4
3. wht-2
4. RAB-7
5. RAB-5
6. LMP-1
7. FYVE
8. wht-7