Extracellular leucine-rich repeat proteins are required to organize the apical extracellular matrix and maintain epithelial junction integrity in C. elegans

Vincent P. Mancuso, Jean M. Parry, Luke Storer, Corey Poggioli, Ken C.Q. Nguyen, David H. Hall, Meera V. Sundaram

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Epithelial cells are linked by apicolateral junctions that are essential for tissue integrity. Epithelial cells also secrete a specialized apical extracellular matrix (ECM) that serves as a protective barrier. Some components of the apical ECM, such as mucins, can influence epithelial junction remodeling and disassembly during epithelial-to-mesenchymal transition (EMT). However, the molecular composition and biological roles of the apical ECM are not well understood. We identified a set of extracellular leucine-rich repeat only (eLRRon) proteins in C. elegans (LET-4 and EGG-6) that are expressed on the apical surfaces of epidermal cells and some tubular epithelia, including the excretory duct and pore. A previously characterized paralog, SYM-1, is also expressed in epidermal cells and secreted into the apical ECM. Related mammalian eLRRon proteins, such as decorin or LRRTM1-3, influence stromal ECM or synaptic junction organization, respectively. Mutants lacking one or more of the C. elegans epithelial eLRRon proteins show multiple defects in apical ECM organization, consistent with these proteins contributing to the embryonic sheath and cuticular ECM. Furthermore, epithelial junctions initially form in the correct locations, but then rupture at the time of cuticle secretion and remodeling of cell-matrix interactions. This work identifies epithelial eLRRon proteins as important components and organizers of the pre-cuticular and cuticular apical ECM, and adds to the small but growing body of evidence linking the apical ECM to epithelial junction stability. We propose that eLRRon-dependent apical ECM organization contributes to cell-cell adhesion and may modulate epithelial junction dynamics in both normal and disease situations.

Original languageEnglish (US)
Pages (from-to)979-990
Number of pages12
JournalDevelopment
Volume139
Issue number5
DOIs
StatePublished - Mar 1 2012

Fingerprint

Extracellular Matrix
Epithelial Cells
leucine-rich repeat proteins
Decorin
Linear Energy Transfer
Epithelial-Mesenchymal Transition
Mucins
Protein C
Cell Adhesion
Leucine
Cell Communication
Ovum
Rupture
Epithelium

Keywords

  • C. elegans
  • Epithelia
  • Extracellular matrix

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Extracellular leucine-rich repeat proteins are required to organize the apical extracellular matrix and maintain epithelial junction integrity in C. elegans. / Mancuso, Vincent P.; Parry, Jean M.; Storer, Luke; Poggioli, Corey; Nguyen, Ken C.Q.; Hall, David H.; Sundaram, Meera V.

In: Development, Vol. 139, No. 5, 01.03.2012, p. 979-990.

Research output: Contribution to journalArticle

Mancuso, Vincent P. ; Parry, Jean M. ; Storer, Luke ; Poggioli, Corey ; Nguyen, Ken C.Q. ; Hall, David H. ; Sundaram, Meera V. / Extracellular leucine-rich repeat proteins are required to organize the apical extracellular matrix and maintain epithelial junction integrity in C. elegans. In: Development. 2012 ; Vol. 139, No. 5. pp. 979-990.
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