The in-silico characterization of the Caenorhabditis elegans matrisome and proposal of a novel collagen classification

Abstract

Proteins are the building blocks of life. While proteins and their localization within cells and sub-cellular compartments are well defined, the proteins predicted to be secreted to form the extracellular matrix - or matrisome - remain elusive in the model organism C. elegans . Here, we used a bioinformatic approach combining gene orthology and protein structure analysis and an extensive curation of the literature to define the C. elegans matrisome. Similar to the human genome, we found that 719 out of ~20,000 genes (~4%) of the C. elegans genome encodes matrisome proteins, including 181 collagens, 35 glycoproteins, 10 proteoglycans, and 493 matrisome-associated proteins. We report that 173 out of the 181 collagen genes are unique to nematodes and are predicted to encode cuticular collagens, which we are proposing to group into five clusters. To facilitate the use of our lists and classification by the scientific community, we developed an automated annotation tool to identify ECM components in large datasets. We also established a novel database of all C. elegans collagens (CeColDB). Last, we provide examples of how the newly defined C. elegans matrisome can be used for annotations and gene ontology analyses of transcriptomic, proteomic, and RNAi screening data. Because C. elegans is a widely used model organism for high throughput genetic and drug screens, and to study biological and pathological processes, the conserved matrisome genes may aid in identifying potential drug targets. In addition, the nematode-specific matrisome may be exploited for targeting parasitic infection of man and crops.

The Matrisome during Aging and Longevity: A Systems-Level Approach toward Defining Matreotypes Promoting Healthy Aging

“…The entire set of proteins that can be expressed by the genome is known as the proteome. The proteome of ECMs has been recently defined for humans, mice, and C. elegans and is called the "matrisome" (http://matrisomeproject.mit.edu; [30,31]). Thus, the matrisome is a subset of the entire proteome dedicated to ECMs [30].…”

“…Thus, the "associated-matrisome" is further divided into secreted factors localizing to ECMs (344 proteins, including transforming growth factor β, bone morphogenetic proteins, Wnts, cytokines), DOI: 10.1159/000504295 ECM-regulators (238 proteins, including the proteases MMPs and cathepsins, the ECM-crosslinkers lysyl oxidases and transglutaminases), and ECM-affiliated (171 proteins, including annexins, semaphorins, syndecans, glypicans, C-type lectins) [30]. The matrisome of humans comprises of 1,027 genes, of mice 1, of 110 genes, and of C. elegans 719 genes, which for each of these organisms is about 4% of their protein-encoding genome [30,31]. The mouse and human matrisome are quite similar, whereas the evolutionary more distant nematode C. elegans shares about 45% of conserved matrisome proteins with humans [31].…”

“…The matrisome of humans comprises of 1,027 genes, of mice 1, of 110 genes, and of C. elegans 719 genes, which for each of these organisms is about 4% of their protein-encoding genome [30,31]. The mouse and human matrisome are quite similar, whereas the evolutionary more distant nematode C. elegans shares about 45% of conserved matrisome proteins with humans [31]. These include proteins usually found in metazoans, such as laminins; collagen types IV, XVIII, and XXV; perlecans; and syndecans [31].…”

“…The mouse and human matrisome are quite similar, whereas the evolutionary more distant nematode C. elegans shares about 45% of conserved matrisome proteins with humans [31]. These include proteins usually found in metazoans, such as laminins; collagen types IV, XVIII, and XXV; perlecans; and syndecans [31]. For instance, human COL25 associated with healthy aging [19] is col-99 in C. elegans [31].…”

“…These include proteins usually found in metazoans, such as laminins; collagen types IV, XVIII, and XXV; perlecans; and syndecans [31]. For instance, human COL25 associated with healthy aging [19] is col-99 in C. elegans [31]. This in silico definition and comprehensive compendium of ECM proteins is key for the analysis of transcriptomic and proteomic datasets in order to identify matrisome gene products associated with young ECM and/or with healthy aging.…”