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Degradomic identification of membrane type 1-matrix metalloproteinase (MT1-MMP/MMP14) as an ADAMTS9 and ADAMTS20 substrate

ABSTRACT: ADAMTS9 and ADAMTS20 are homologous secreted proteases implicated in ECM proteolysis and ciliogenesis, but few relevant substrates of these proteases are currently known. Quantitative N-terminomics comparison of RPE-1 cells lacking ADAMTS9 with parental RPE-1 cells identified transmembrane protease MT1-MMP (MMP14) as a novel ADAMTS9 substrate. The resulting enhanced cell-surface MT1-MMP activity in the gene-edited cells contributes to their adhesion defect, but not lack of cilia. A key physiological function of ADAMTS9/20 may be to dampen cell-surface MT1-MMP activity.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Daniel Martin

LAB HEAD: Suneel Apte

PROVIDER: PXD036612 | Pride | 2023-07-20

REPOSITORIES: Pride

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			Action	DRS
	Lum_18mar1205-_1_.mzML	Mzml
	Lum_18mar1205-_1_.mzid.gz	Mzid
	Lum_18mar1205-_1_.pdResult	Other
	Lum_18mar1205-_1__Lysates_Master_sheet.xlsx	Xlsx
	Lum_18mar1205.raw	Raw

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Degradomic Identification of Membrane Type 1-Matrix Metalloproteinase as an ADAMTS9 and ADAMTS20 Substrate.

Nandadasa Sumeda S Martin Daniel D Deshpande Gauravi G Robert Karyn L KL Stack M Sharon MS Itoh Yoshifumi Y Apte Suneel S SS

Molecular & cellular proteomics : MCP 20230509 6

The secreted metalloproteases ADAMTS9 and ADAMTS20 are implicated in extracellular matrix proteolysis and primary cilium biogenesis. Here, we show that clonal gene-edited RPE-1 cells in which ADAMTS9 was inactivated, and which constitutively lack ADAMTS20 expression, have morphologic characteristics distinct from parental RPE-1 cells. To investigate underlying proteolytic mechanisms, a quantitative terminomics method, terminal amine isotopic labeling of substrates was used to compare the parenta ...[more]

PMID: 37169079

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