Worm Breeder's Gazette 13(4): 35 (October 1, 1994)

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.

sum-1 Encodes a Protein Containing Seven Transmembrane Domains.

Diane Levitan, Iva Greenwald

HHMI, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032

  sum-1 mutants have essentially normal VPC lineages but have abnormal vulval
morphogenesis and are Egl- (WBG vol. l2 ,no. 2 and vol. 12, no. 5). Approximately
50% of sum-1 mutant animals have a large blip at the vulva. We have further
examined the morphology of the adult vulva in the remaining 50% of animals that do
not form a vulval blip. In wild type, the vulval lips invaginate inward but in sum-1
mutant animals the vulva looks flat across the bottom, giving it a closed appearance.
This phenotype may be another manifestation of an underlying defect in
  The sequence analysis of sum-1 has provided an insight into its biochemical
function. We cloned sum-1 by transformation rescue and identified a 3.5 kb genomic
fragment that fully rescues the sum-1 mutant phenotype. We isolated cDNAs
corresponding to this genomic fragment and determined their sequence. The sum-1
transcript is 1.5 kb long and has the potential to encode a protein containing seven
transmembrane spanning regions. We found no obvious signal sequence in the
predicted sum-1 protein; the absence of a signal sequence has been observed in a
number of other seven transmembrane domain proteins. The only three putative
glycosylation sites in sum-1 are located between the fifth and sixth
membrane-spanning regions. If these glycosylation sites are placed extracellularly,
the amino terminus of sum-1 would reside inside of the cell. This would be an
unusual orientation for a seven transmembrane domain receptor.
  sum-1 is 48% identical to the predicted protein from a human cDNA, isolated as
part of the Human Genome project, so it has been evolutionarily conserved. sum-1
has no significant homology to most proteins in several databases and therefore may
represent a distantly related member of the seven transmembrane domain receptor
superfamily. Alternatively, sum-1 may be an integral membrane protein that does not
function as a receptor. For example, it may function as a ligand (e.g. boss from
Drosophila), or have some other function not yet described for seven transmembrane
domain proteins.
  An intriguing possibility is that sum-1 plays a role in a signalling event that is
involved in specifying the terminal differentiated state of the vulva cells and/or in
assembly or function of the vulval toroidal rings. Consistent with this role,
preliminary examination of a sum-1 ::lacZreporter construct shows it is expressed in a
subset of vulval cells during the L4 stage. This late intercellular signalling among the
vulval cells may also involve lin-12 .A lin-12 ::lacZreporter construct is also normally
expressed in a subset of cells in the L4 vulva (Wilkinson and Greenwald, unpublished
observations) and may be responsible for the "late" Egl defect of lin-12 hypomorphs
(Sundaram and Greenwald (1993) Genetics 135. p. 755-763). The pattern of lin-12
::lacZexpression is aberrant in a sum-1 mutant background. Expression is completely
eliminated in 50% of the animals examined or present only in a subset of cells in the
other 50%. sum-1 activity may play a direct role in maintaining lin-12 expression or
an indirect role via effects on cell fates.