ADAM10 is Expressed by Ameloblasts, Cleaves the RELT TNF Receptor Extracellular Domain and Facilitates Enamel Development.

Abstract

MMP20 cleaves cadherins and may facilitate cell movement, however MMP20 is not known to cleave tight junction or desmosome proteins. Ameloblasts had not previously been screened for membrane anchored proteases that could contribute to cell movement. Here we performed a PCR screen for proteolyticlly active A Disintegrin And Metalloproteinase (ADAM) family members. These proteinases are termed sheddases because they have a transmembrane domain and their catalytic domain on the cell surface can function to release anchored proteins. Significantly, ADAMs can be targeted to specific substrates on the cell membrane through their interaction with tetraspanins. Six ADAMs (ADAM8, 9, 10, 15, 17, 19) were expressed in mouse enamel organs. We show that Adam10 expression begins in the apical loop, continues through the secretory stage and abruptly ends at the transition stage when ameloblast migration ceases. ADAM10 cleaves cadherins and tight junction plus desmosome proteins and is well characterized for its role in cell movement. ADAM10 facilitated LS8 cell migration/invasion through a Matrigel coated membrane and we demonstrate that ADAM10, but not ADAM17 cleaves the RELT extracellular domain. This striking result is significant because RELT mutations cause amelogenesis imperfecta (AI) and this directly links ADAM10 to an important role in enamel development.

• Authors: Atsushi Ikeda, Shifa Shahid, Benjamin R Blumberg, Maiko Suzuki, John D Bartlett
• Journal: Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 14086 (Oct 01 2019) ISSN: 2045-2322 [Electronic] England
• PMID: 31575895 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Receptors, Tumor Necrosis Factor
• Relt protein, mouse
• Amyloid Precursor Protein Secretases
• ADAM10 Protein
• Adam10 protein, mouse

Topics

• ADAM10 Protein (metabolism, physiology)
• Ameloblasts (metabolism)
• Amyloid Precursor Protein Secretases (metabolism, physiology)
• Animals
• Blotting, Western
• Cell Movement
• Dental Enamel (growth & development, metabolism)
• Fluorescent Antibody Technique
• In Situ Hybridization
• Membrane Proteins (metabolism, physiology)
• Mice
• Real-Time Polymerase Chain Reaction
• Receptors, Tumor Necrosis Factor (metabolism)