Abstract
Matrix metalloprotease (MMP) genes encode endopeptidases that cleave protein components of the extracellular matrix (ECM) as well as non-ECM proteins. Here we report the results of a comprehensive survey of MMPs in the laboratory axolotl and other representative salamanders. Surprisingly, 28 MMPs were identified in salamanders and 9 MMP paralogs were identified as unique to the axolotl and other salamander taxa, with several of these presenting atypical amino acid insertions not observed in other tetrapod vertebrates. Furthermore, as assessed by sequence information, all of the novel salamander MMPs are of the secreted type, rather than cell membrane anchored. This suggests that secreted type MMPs expanded uniquely within salamanders to presumably execute catalytic activities in the extracellular milieu. To facilitate future studies of salamander-specific MMPs, we annotated transcriptional information from published studies of limb and tail regeneration. Our analysis sets the stage for comparative studies to understand why MMPs expanded uniquely within salamanders.
Highlights
A comprehensive survey of Matrix metalloprotease (MMP) genes from available axolotl transcriptomic, genomic and EST databases, along with targeted sequencing of presumptive axolotl novel MMPs genes, yielded a total of 28 MMPs (Supplementary Table 1). This number exceeds the number of MMPs identified for other tetrapods, including anciently duplicated teleost genomes (26 MMPs are known for zebrafish) (Pedersen et al, 2015). This survey shows that the axolotl has an expanded number of MMP paralogs, the highest number recorded for any species
We examined the evolutionary history of MMPs using 268 complete MMP protein coding sequences from 19 vertebrate species: (A) 10 salamander species: the axolotl (Ambystoma mexicanum (Amex), Ambystoma andersoni (Aand), Ambystoma texanum (Atex), Ambystoma laterale (Alat), Ambystoma tigrinum (Atig), Hynobius chinensis (Hchi), Pleurodeles waltl (Pwal), Nothophthalmus viridescens (Nvir), Bolitoglossa ramose (Bram), Cynops pyrrhogaster (Cpyr), (B) three caecilians [Rhinatrema bivittatum (Rbiv), Typhlonectes compressicaud (Tcom), Microcaecilia unicolor (Muni)], (C) Xenopus tropicalis (Xtro), (D) Gallus gallus (Ggal), (E) Mus musculus (Mmus), (F) Homo sapiens (Hsap), and (G) Latimeria chalumnae (Lcha) as a tetrapod outgroup (Figure 2 and Supplementary Table 1)
We found that salamander novel MMPs (MMP3/10 A-E, MMPe) have unique salamander-specific insertions and substitutions not found in other tetrapod MMPs
Summary
MMPs constitute a large family (24 members in human) of Zn+2 dependent proteases that cleave ECM and non-ECM proteins whose functions are associated with many different biological processes, including ECM remodeling, morphogenesis and tissue repair (Nagase et al, 2006; Gill and Parks, 2007; Huxley-Jones et al, 2007; Page-McCaw et al, 2007; Fanjul-Fernández et al, 2010; Jackson et al, 2010; Löffek et al, 2011). Secreted MMPs include: (A) Archetypal MMPs: collagenases (MMP1, 8, 13), stromelysins (MMP3, 10), and others (MMP12, 19, 20), (B) Gelatinases (MMP2, 9), (C) Matrilysins (MMP7, 26), and (D) Furin-activated secreted MMPs (MMP11, 21, 28) Most of these secreted MMPs present the same domain structures, including a signaling peptide, a pro-peptide that contains a cysteine switch (PCRGVPD), a catalytic domain. Most of the membrane-anchored MMPs present the aforementioned domains and have extra transmembrane domains that allow further classification into: (A) Transmembrane domain I containing (MMP14, 15, 16, 24), (B) GPI anchored (MMP17, 25), and (C) Transmembrane domain II containing (MMP23) which lack the conserved cysteine switch Given their critical activities in ECM homeostasis and remodeling, which in turn influences cell migration, angiogenesis, proliferation and differentiation, MMP activities are under tight regulation. Activated MMPs are regulated by tissue inhibitors of MMPs (TIMP) enzymes that are generally thought to inhibit MMP catalytic functions (Nagase et al, 2006; Gill and Parks, 2007; Huxley-Jones et al, 2007)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
