Worm Breeder's Gazette 15(3): e3 (June 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.


Leexan Hong, Beth K. Gatewood, James T. Ward, Elizabeth A. Bucher

University of Pennsylvania, Department of Cell and Developmental Biology, School of Medicine, Philadelphia, PA 19104-6058

We are investigating the functions of mup-4, a member of a new family of
genes, that mediate cell-cell and/or cell-matrix interactions in
Caenorhabditis elegans.  The mup-4 and mua-3 genes (J. Plenefisch and E.
Hedgecock, pers. comm.) have recently been cloned and are shown to be
related proteins.  Mutants for these genes show related, but distinct
phenotypes: mup-4 mutants have defects in embryonic epidermal integrity
and muscle position (2), whereas mua-3 mutants, identified by us (1, 2),
as well as by J. Plenefisch and E. Hedgecock (pers. comm.), display
muscle position defects that occur during larval stages.  mup-4 and
mua-3 both encode large transmembrane proteins, which include large
novel intracellular domains (largely unrelated between the two) and an
extracellular domain containing many EGF-like repeats, a type XII
collagen motif, and a shared, novel twice-repeated sequence (4).  MUA-3
is larger and includes more EGF-like repeats as well as some LDL-like
repeats.  Although MUP-4 and MUA-3 represent a novel class of proteins,
they are similar to many other extracellular matrix (ECM), cell adhesion
and cell signaling molecules in that they have a complex modular
structure.  For example, the combination of EGF-like repeats between
type XII collagen-like elements has been observed in vertebrate collagen
matrix protein (CMP), present at tendons, but CMP is a secreted ECM
protein.  The specific functions of these ECM domains, included in MUA-3
and MUP-4, are poorly understood (e.g., 3). 

Thus, based on its predicted protein domain structure and mutant
phenotype, MUP-4 could function as a signal, a receptor, and/or a cell
adhesion molecule.  One possibility is that MUP-4 mediates cell-cell
adhesion and/or signaling between neighboring hypodermal cells, the
extracellular domains mediating interactions with adjacent hypodermal
cell proteins, and the intracellular domains functioning to anchor or
signal to cytoskeletal structures.  Another possibility is that MUP-4,
through the collagen XII domains, interacts directly with the ECM,
either basally to the basement membrane and/or apically to the cuticle,
which then would function to anchor the hypodermis to the ECM and
directly or indirectly maintain muscle attachments.  It is also possible
that MUP-4 mediates several of the above functions via its modular and
complex structure.  We are currently testing these hypotheses by: (i)
determining the temporal, spatial and subcellular localization of MUP-4;
(ii) examining the ultrastructural defects in mup-4 mutants; and (iii)
testing for genetic interactions with mutations in ECM proteins (e.g.,
perlecan, type IV collagens, cuticular collagens), adhesion proteins
(e.g., catenins/cadherins), and muscle attachment proteins (e.g.,

1. Bucher, E., and I. Greenwald. 1991. A genetic mosaic screen of
essential zygotic genes in Caenorhabditis elegans. Genetics. 128:281-92.
2. Gatewood, B. K., and E. A. Bucher. 1997. The mup-4 locus in
Caenorhabditis elegans is essential for hypodermal integrity, organismal
morphogenesis and embryonic body wall muscle position. Genetics.
3. Wagener, R., B. Kobbe, and M. Paulsson. 1997. Primary structure of
matrilin-3, a new member of a family of extracellular matrix proteins
related to cartilage matrix protein (matrilin-1) and von Wildebrand
factor. FEBS Letters. 413:129-134.
4. Wilson, R., R. Ainscough, K. Anderson, C. Baynes, M. Berks, J.
Bonfield, J. Burton, M. Connell, T. Copsey, J. Cooper, and et al. 1994.
2.2 Mb of contiguous nucleotide sequence from chromosome III of C.
elegans [see comments]. Nature. 368:32-8.