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The short coiled-coil domain-containing protein UNC-69 cooperates with UNC-76 to regulate axonal outgrowth and normal presynaptic organization in Caenorhabditis elegans

Cheng-Wen Su1,2* email, Suzanne Tharin3,4,10* email, Yishi Jin5 email, Bruce Wightman6 email, Mona Spector4 email, David Meili1,7,11 email, Nancy Tsung8,12 email, Christa Rhiner1,2 email, Dimitris Bourikas2,7 email, Esther Stoeckli2,7 email, Gian Garriga9 email, H Robert Horvitz8 email and Michael O Hengartner1,2 email

1  Institute for Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland

2  Neuroscience Center Zurich, ETH and University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland

3  Program in Genetics, SUNY at Stony Brook, Stony Brook, NY 11794, USA

4  Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA

5  Howard Hughes Medical Institute, Department of Molecular, Cellular and Developmental Biology, Sinsheimer Laboratories, University of California, Santa Cruz, CA 95064, USA

6  Biology Department, Muhlenberg College, Allentown, PA 18104, USA

7  Zoological Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland

8  Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

9  Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA

10  Current address: Department of Neurosurgery, Brigham and Women's Hospital, Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA

11  Current address: Abteilung für Klinische Chemie und Biochemie, Universitäts-Kinderklinik, Steinwiesstrasse 75, CH-8032 Zürich, Switzerland

12  Current address: Clinigen, Inc., 400 W. Cummings Park #5700, Woburn, MA 01801, USA

author email corresponding author email* Contributed equally

Journal of Biology 2006, 5:9doi:10.1186/jbiol39

Published: 25 May 2006

Abstract

Background

The nematode Caenorhabditis elegans has been used extensively to identify the genetic requirements for proper nervous system development and function. Key to this process is the direction of vesicles to the growing axons and dendrites, which is required for growth-cone extension and synapse formation in the developing neurons. The contribution and mechanism of membrane traffic in neuronal development are not fully understood, however.

Results

We show that the C. elegans gene unc-69 is required for axon outgrowth, guidance, fasciculation and normal presynaptic organization. We identify UNC-69 as an evolutionarily conserved 108-amino-acid protein with a short coiled-coil domain. UNC-69 interacts physically with UNC-76, mutations in which produce similar defects to loss of unc-69 function. In addition, a weak reduction-of-function allele, unc-69(ju69), preferentially causes mislocalization of the synaptic vesicle marker synaptobrevin. UNC-69 and UNC-76 colocalize as puncta in neuronal processes and cooperate to regulate axon extension and synapse formation. The chicken UNC-69 homolog is highly expressed in the developing central nervous system, and its inactivation by RNA interference leads to axon guidance defects.

Conclusion

We have identified a novel protein complex, composed of UNC-69 and UNC-76, which promotes axonal growth and normal presynaptic organization in C. elegans. As both proteins are conserved through evolution, we suggest that the mammalian homologs of UNC-69 and UNC-76 (SCOCO and FEZ, respectively) may function similarly.

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