Worm Breeder's Gazette 15(2): 38 (February 1, 1998)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

Ce-TOR on the road to growth?

Carmen Spycher, Fritz Muller

Institute of Zoology, University of Fribourg, Perolles, CH-1700 Fribourg, Switzerland

TOR (target of rapamycin) belongs to a family of proteins which has a
carboxy-terminal domain similar to catalytic domains of lipid kinases.
Members of this family (ATM-like proteins: MEC1, TEL1, RAD3, MEI-41,
ATM, DNA-PK and TOR) are involved in cell-cycle regulation, DNA repair
and recombination. TOR proteins were first discovered in yeast (TOR1 and
TOR2) and homologs have now been found in mammals
(FRAP/RAFT1/RAPT1/mTOR). None of these proteins seem to have a lipid
kinase activity, but for some a protein kinase activity has been shown.

We have found a gene encoding a TOR homolog in C. elegans (Ce-tor) on
cosmid B0261 (on chromosome I) by searching the C. elegans database. The
Ce-tor mRNA is SL-1 transspliced, has a length of about 8.6 kb and
includes 32 exons. Its putative protein product has a length of 2695 aa.
It is most homologous to mammalian TORs: over the whole length 39% and
in the lipid kinase motif, the most conserved region, 72% of the amino
acids are identical to FRAP. Ce-TOR has all the essential amino acids
found in a lipid kinase motif (ATP-binding motif similar to protein
kinases and putative catalytic-/substrate-binding site) and it also
contains the unique carboxyl-terminal region typical for ATM-like
Antisense-injection experiments with RNA produced from the cDNA clone
yk31h11 indicated that Ce-tor is an essential gene. Progeny of injected
wild-type worms showed multiple defects: slow growing and occasional
arrest at larval stages, reduced fertility, a protrusion at the vulva
(rarely also at the anus), and slight uncoordinated movement. In yeast,
TOR1 and TOR2 activate translation initiation in response to nutrients
and the cells progress through G1 of the cell-cycle. Mammalian TORs play
a similar role. TOR2, but not TOR1, is involved in the organisation of
the actin cytoskeleton in a cell-cycle dependent manner. It is therefore
essential for growth.

Currently we are performing rescuing experiments with some lethal
mutations (provided by A. M. Rose) mapping between dpy-5 and unc-13. We
are producing antibodies against Ce-TOR to study the expression pattern
and to determine, if this protein has a specific rather than a
housekeeping function.