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First published online 10 January 2007
doi: 10.1242/dev.02767

Development 134, 691-702 (2007)
Published by The Company of Biologists 2007
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SEL-2, the C. elegans neurobeachin/LRBA homolog, is a negative regulator of lin-12/Notch activity and affects endosomal traffic in polarized epithelial cells

Natalie de Souza1, Laura G. Vallier1,2, Hanna Fares1,3 and Iva Greenwald1,*

1 Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, 701 W. 168th Street, Hammer Health Sciences, New York, NY 10032, USA.
2 Department of Biology, Hofstra University, Gittleson Hall Room 103, Hempstead, NY 11549, USA.
3 Department of Molecular and Cellular Biology, University of Arizona, Life Sciences South, Room 531, 1007 E. Lowell Street, Tucson, AZ 85721, USA.

* Author for correspondence (e-mail: dev.gree{at}cancercenter.columbia.edu)

Accepted 30 November 2006

The vulval precursor cells (VPCs) of Caenorhabditis elegans are polarized epithelial cells that adopt a precise pattern of fates through regulated activity of basolateral LET-23/EGF receptor and apical LIN-12/Notch. During VPC patterning, there is reciprocal modulation of endocytosis and trafficking of both LET-23 and LIN-12. We identified sel-2 as a negative regulator of lin-12/Notch activity in the VPCs, and found that SEL-2 is the homolog of two closely related human proteins, neurobeachin (also known as BCL8B) and LPS-responsive, beige-like anchor protein (LRBA). SEL-2, neurobeachin and LRBA belong to a distinct subfamily of BEACH-WD40 domain-containing proteins. Loss of sel-2 activity leads to basolateral mislocalization and increased accumulation of LIN-12 in VPCs in which LET-23 is not active, and to impaired downregulation of basolateral LET-23 in VPCs in which LIN-12 is active. Downregulation of apical LIN-12 in the VPC in which LET-23 is active is not affected. In addition, in sel-2 mutants, the polarized cells of the intestinal epithelium display an aberrant accumulation of the lipophilic dye FM4-64 when the dye is presented to the basolateral surface. Our observations indicate that SEL-2/neurobeachin/LRBA is involved in endosomal traffic and may be involved in efficient delivery of cell surface proteins to the lysosome. Our results also suggest that sel-2 activity may contribute to the appropriate steady-state level of LIN-12 or to trafficking events that affect receptor activation.

Key words: LIN-12, Notch, BEACH, Endocytosis, Caenorhabditis elegans


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Development 2007 134: e402. [Full Text]  



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