Functions of KLK4 and MMP-20 in dental enamel formation

Abstract

Two proteases are secreted into the enamel matrix of developing teeth. The early protease is enamelysin . The late protease is kallikrein 4 (KLK4). Mutations in MMP20 and KLK4 both cause autosomal recessive amelogenesis imperfecta, a condition featuring soft, porous enamel containing residual protein. MMP-20 is secreted along with enamel proteins by secretory stage ameloblasts. Enamel protein cleavage products accumulate in the space between the crystal ribbons, helping to support them. MMP-20 steadily cleaves accumulated enamel proteins, so their concentration decreases with depth. Kallikrein 4 is secreted by transition and maturation stage ameloblasts. KLK4 aggressively degrades the retained organic matrix following the termination of enamel protein secretion. The principle functions of MMP-20 and KLK4 in dental enamel formation are to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins.

Kallikrein-related peptidases in prostate, breast, and ovarian cancers: from pathobiology to clinical relevance

“…The regulated tissue-specifi c expression and activation of KLKs enable them to participate in a great number of diverse physiological procedures, such as the regulation of blood pressure (KLK1-mediated cleavage of kininogenase) (Bhoola et al , 1992 ), semen liquefaction (PSA/KLK3-and KLK2-mediated cleavage of semenogelins) (Pampalakis and Sotiropoulou , 2007 ), skin desquamation (KLK5-, KLK7-, and KLK14-mediated digestion of desmoglein, desmocollin, corneodesmosin) (Borgono et al , 2007a ), tooth maturation (KLK4-mediated processing of enamelin) (Lu et al , 2008 ), and innate immunity (KLK5-and KLK7-mediated activation of cathelicidin antimicrobial peptide) (Yamasaki et al , 2006 ). Bearing in mind the irreversible impact of proteases upon their substrates, as well as the launch of downstream enzyme cascades that lead to the amplifi cation of the initial stimuli, the regulation of KLKs activity becomes crucial for their benefi cial physiological function.…”

Sweetened kallikrein-related peptidases (KLKs): glycan trees as potential regulators of activation and activity

“…This observation cannot be easily explained, since these three potential N-glycosylation sites are located at the molecular surface opposite to the active site, which was suggested previously and is illustrated in the structure-based alignment (Figure 2) (Scully et al, 1998). Possibly, the N-glycans protect pKLK4 from auto-degradation (Lu et al, 2008). Recently, a systematic analysis of porcine and murine glyco-KLK4 isolated from teeth found bi-and triantennary N-glycan trees on both enzymes (Yamakoshi et al, 2011 of GlcNAc-Gal-Sia.…”

“…As protease with a strong tryptic preference, KLK4 degrades matrix proteins during enamel formation and could be an activator of KLK2 and 3 in seminal fluid and of several other KLKs (Lu et al, 2008;Yoon et al, 2009). A nonsense mutation at the Trp141 codon to a stop codon in the fourth exon and a frameshift mutation at the Gly69 codon of the human KLK4 gene result in truncated KLK4 variants lacking the catalytic Ser195 and subsequently in improper enamel formation, termed amelogenesis imperfecta (Hart et al, 2004;Wang et al, 2013).…”

Molecular mechanisms of odontogenesis

“…Секретируется амелобластами в стадии вызревания. Является составляющей базальной пластинки между аме-лобластами [Moffatt, Iwasaki] Модель не разработана Энамелизин (MMP-20) Экспрессируется от начала секреторной стадии до начала стадии вызревания [24]. Активирует амелогенин за счет протеолиза C-конца, обе-спечивая реакцию амелогенина и гидроксиапатита.…”