scholarly journals Diversification of metazoan Kexin-like proprotein convertases: insights from the leech Helobdella

2019 ◽  
Author(s):  
Wei-Yu Tao ◽  
Ya-Chih Cheng ◽  
Mi Hye Song ◽  
David A. Weisblat ◽  
Dian-Han Kuo

AbstractIntercellular communication is quintessential for multicellularity and often mediated by secreted peptide ligands. In Metazoa, proprotein convertases are a major class of endoproteases partaking in the proteolytic processing of these ligands, which is in turn required for their signaling activities. In vertebrates, the best-studied convertase substrates are neuropeptides, peptide hormones, and members of the TGFβ/BMP-family. Each ligand is processed by a particular subset of convertases. Therefore, the diversification of convertases may have contributed to the growing complexity of cellular communication in metazoan evolution. However, proprotein convertases have not been systematically explored in Metazoa. Here, we sampled the representative metazoan genomes and established that six Kexin-like proprotein convertases were present in the last common ancestor of protostomes and deuterostomes. Among these, we identified a novel PCSKX orthologous group (OG) that was lost in vertebrates. Spiralian protosomes have, in general, maintained all six OGs. Therefore, we characterized the functional divergence of the Kexin-like OGs in the leech Helobdella, an experimentally tractable spiralian. Gene expression patterns suggested that PCSK1 and PCSK2 are specialized for the processing of neuropeptides and peptide hormones in bilaterians and that the newly identified PCSKX is probably functionally similar to furin and PCSK7. Finally, we showed that, distinct from the BMP morphogen in vertebrate embryos, the convertase-mediated proteolytic cleavage is not required for the short-range BMP signaling in the dorsoventral patterning of leech ectoderm. Together, our data revealed the complexity of the Kexin-like proprotein convertase gene family and their roles in generating diverse patterns of cellular communication in Metazoa.

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Weihua Su ◽  
Yongjuan Ren ◽  
Dongjiao Wang ◽  
Long Huang ◽  
Xueqin Fu ◽  
...  

Abstract Background Calcineurin B-like protein (CBL)-interacting protein kinases (CIPKs) are the primary components of calcium sensors, and play crucial roles in plant developmental processes, hormone signaling transduction, and in the response to exogenous stresses. Results In this study, 48 CIPK genes (SsCIPKs) were identified from the genome of Saccharum spontaneum. Phylogenetic reconstruction suggested that the SsCIPK gene family may have undergone six gene duplication events from the last common ancestor (LCA) of SsCIPKs. Whole-genome duplications (WGDs) served as the driving force for the amplification of SsCIPKs. The Nonsynonymous to synonymous substitution ratio (Ka/Ks) analysis showed that the duplicated genes were possibly under strong purifying selection pressure. The divergence time of these duplicated genes had an average duplication time of approximately 35.66 Mya, suggesting that these duplication events occurred after the divergence of the monocots and eudicots (165 Mya). The evolution of gene structure analysis showed that the SsCIPK family genes may involve intron losses. Ten ScCIPK genes were amplified from sugarcane (Saccharum spp. hybrids). The results of real-time quantitative polymerase chain reaction (qRT-PCR) demonstrated that these ten ScCIPK genes had different expression patterns under abscisic acid (ABA), polyethylene glycol (PEG), and sodium chloride (NaCl) stresses. Prokaryotic expression implied that the recombinant proteins of ScCIPK3, − 15 and − 17 could only slightly enhance growth under salinity stress conditions, but the ScCIPK21 did not. Transient N. benthamiana plants overexpressing ScCIPKs demonstrated that the ScCIPK genes were involved in responding to external stressors through the ethylene synthesis pathway as well as to bacterial infections. Conclusions In generally, a comprehensive genome-wide analysis of evolutionary relationship, gene structure, motif composition, and gene duplications of SsCIPK family genes were performed in S. spontaneum. The functional study of expression patterns in sugarcane and allogenic expressions in E. coli and N. benthamiana showed that ScCIPKs played various roles in response to different stresses. Thus, these results improve our understanding of the evolution of the CIPK gene family in sugarcane as well as provide a basis for in-depth functional studies of CIPK genes in sugarcane.


2007 ◽  
Vol 30 (4) ◽  
pp. 77
Author(s):  
Y. Y. Chen ◽  
C. L. Hehr ◽  
K. Atkinson-Leadbeater ◽  
J. C. Hocking ◽  
S. McFarlane

Background: The growth cone interprets cues in its environment in order to reach its target. We want to identify molecules that regulate growth cone behaviour in the developing embryo. We investigated the role of A disintegrin and metalloproteinase 10 (ADAM10) in axon guidance in the developing visual system of African frog, Xenopus laevis. Methods: We first examined the expression patterns of adam10 mRNA by in situ hybridization. We then exposed the developing optic tract to an ADAM10 inhibitor, GI254023X, in vivo. Lastly, we inhibited ADAM10 function in diencephalic neuroepithelial cells (through which retinal ganglion cell (RGC) axons extend) or RGCs by electroporating or transfecting an ADAM10 dominant negative (dn-adam10). Results: We show that adam10 mRNA is expressed in the dorsal neuroepithelium over the time RGC axons extend towards their target, the optic tectum. Second, pharmacological inhibition of ADAM10 in an in vivo exposed brain preparation causes the failure of RGC axons to recognize their target at low concentrations (0.5, 1 μM), and the failure of the axons to make a caudal turn in the mid-diencephalon at higher concentration (5 μM). Thus, ADAM10 function is required for RGC axon guidance at two key guidance decisions. Finally, molecular inhibition of ADAM10 function by electroporating dn-adam10 in the brain neuroepithelium causes defects in RGC axon target recognition (57%) and/or defects in caudal turn (12%), as seen with the pharmacological inhibitor. In contrast, molecular inhibition of ADAM10 within the RGC axons has no effect. Conclusions: These data argue strongly that ADAM10 acts cell non-autonomously within the neuroepithelium to regulate the guidance of RGC axons. This study shows for the first time that a metalloproteinase acts in a cell non-autonomous fashion to direct vertebrate axon growth. It will provide important insights into candidate molecules that could be used to reform nerve connections if destroyed because of injury or disease. References Hattori M, Osterfield M, Flanagan JG. Regulated cleavage of a contact-mediated axon repellent. Science 2000; 289(5483):1360-5. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M, Nikolov DB. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 2005; 123(2):291-304. Pan D, Rubin GM. Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell 1997; 90(2):271-80.


Animals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 873 ◽  
Author(s):  
Jun Cao ◽  
Xiuzhu Cheng

Cytochrome P450s (CYPs) are a family of membrane-bound mono-oxygenase proteins, which are involved in cell metabolism and detoxification of various xenobiotic substances. In this study, we identified 58 putative CYP genes in Amur stickleback (Pungitius sinensis) based on the transcriptome sequencing. Conserved motif distribution suggested their functional relevance within each group. Some present recombination events have accelerated the evolution of this gene family. Moreover, a few positive selection sites were identified, which may have accelerated the functional divergence of this family of proteins. Expression patterns of these CYP genes were investigated and indicated that most were affected by dimethoate treatment, suggesting that CYPs were involved in the detoxication of dimethoate. This study will provide a foundation for the further functional investigation of CYP genes in fishes.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhixuan Du ◽  
Qitao Su ◽  
Zheng Wu ◽  
Zhou Huang ◽  
Jianzhong Bao ◽  
...  

AbstractMultidrug and toxic compound extrusion (MATE) proteins are involved in many physiological functions of plant growth and development. Although an increasing number of MATE proteins have been identified, the understanding of MATE proteins is still very limited in rice. In this study, 46 MATE proteins were identified from the rice (Oryza sativa) genome by homology searches and domain prediction. The rice MATE family was divided into four subfamilies based on the phylogenetic tree. Tandem repeats and fragment replication contribute to the expansion of the rice MATE gene family. Gene structure and cis-regulatory elements reveal the potential functions of MATE genes. Analysis of gene expression showed that most of MATE genes were constitutively expressed and the expression patterns of genes in different tissues were analyzed using RNA-seq. Furthermore, qRT-PCR-based analysis showed differential expression patterns in response to salt and drought stress. The analysis results of this study provide comprehensive information on the MATE gene family in rice and will aid in understanding the functional divergence of MATE genes.


1995 ◽  
Vol 16 (4) ◽  
pp. 322-361 ◽  
Author(s):  
Yves Rouillé ◽  
Stephen J. Duguay ◽  
Kaare Lund ◽  
Machi Furuta ◽  
Qiuming Gong ◽  
...  

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4439-4447 ◽  
Author(s):  
Juan Larraín ◽  
Michael Oelgeschläger ◽  
Nan I. Ketpura ◽  
Bruno Reversade ◽  
Lise Zakin ◽  
...  

Dorsoventral patterning is regulated by a system of interacting secreted proteins involving BMP, Chordin, Xolloid and Twisted gastrulation (Tsg). We have analyzed the molecular mechanism by which Tsg regulates BMP signaling. Overexpression of Tsg mRNA in Xenopus embryos has ventralizing effects similar to Xolloid, a metalloprotease that cleaves Chordin. In embryos dorsalized by LiCl treatment, microinjection of Xolloid or Tsg mRNA restores the formation of trunk-tail structures, indicating an increase in BMP signaling. Microinjection of Tsg mRNA leads to the degradation of endogenous Chordin fragments generated by Xolloid. The ventralizing activities of Tsg require an endogenous Xolloid-like activity, as they can be blocked by a dominant-negative Xolloid mutant. A BMP-receptor binding assay revealed that Tsg has two distinct and sequential activities on BMP signaling. First, Tsg makes Chordin a better BMP antagonist by forming a ternary complex that prevents binding of BMP to its cognate receptor. Second, after cleavage of Chordin by Xolloid, Tsg competes the residual anti-BMP activity of Chordin fragments and facilitates their degradation. This molecular pathway, in which Xolloid switches the activity of Tsg from a BMP antagonist to a pro-BMP signal once all endogenous full-length Chordin is degraded, may help explain how sharp borders between embryonic territories are generated.


2021 ◽  
Author(s):  
Pengcheng Ma ◽  
Xingyan Liu ◽  
Huimin Liu ◽  
Zaoxu Xu ◽  
Xiangning Ding ◽  
...  

Abstract Vertebrate evolution was accompanied with two rounds of whole genome duplication followed by functional divergence in terms of regulatory circuits and gene expression patterns. As a basal and slow-evolving chordate species, amphioxus is an ideal paradigm for exploring the origin and evolution of vertebrates. Single cell sequencing has been widely employed to construct the developmental cell atlas of several key species of vertebrates (human, mouse, zebrafish and frog) and tunicate (sea squirts). Here, we performed single-nucleus RNA sequencing (snRNA-seq) and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) for different stages of amphioxus (covering embryogenesis and adult tissues). With the datasets generated we constructed the developmental tree for amphioxus cell fate commitment and lineage specification, and revealed the underlying key regulators and genetic regulatory networks. The generated data were integrated into an online platform, AmphioxusAtlas, for public access at http://120.79.46.200:81/AmphioxusAtlas.


Development ◽  
1992 ◽  
Vol 116 (2) ◽  
pp. 335-346 ◽  
Author(s):  
M. Freeman ◽  
B.E. Kimmel ◽  
G.M. Rubin

In order to identify potential target genes of the rough homeodomain protein, which is known to specify some aspects of the R2/R5 photoreceptor subtype in the Drosophila eye, we have carried out a search for enhancer trap lines whose expression is rough-dependent. We crossed 101 enhancer traps that are expressed in the developing eye into a rough mutant background, and have identified seven lines that have altered expression patterns. One of these putative rough target genes is rhomboid, a gene known to be required for dorsoventral patterning and development of some of the nervous system in the embryo. We have examined the role of rhomboid in eye development and find that, while mutant clones have only a subtle phenotype, ectopic expression of the gene causes the non-neuronal mystery cells to be transformed into photoreceptors. We propose that rhomboid is a part of a partially redundant network of genes that specify photoreceptor cell fate.


Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3815-3828 ◽  
Author(s):  
C.T. Miller ◽  
T.F. Schilling ◽  
K. Lee ◽  
J. Parker ◽  
C.B. Kimmel

Mutation of sucker (suc) disrupts development of the lower jaw and other ventral cartilages in pharyngeal segments of the zebrafish head. Our sequencing, cosegregation and rescue results indicate that suc encodes an Endothelin-1 (Et-1). Like mouse and chick Et-1, suc/et-1 is expressed in a central core of arch paraxial mesoderm and in arch epithelia, both surface ectoderm and pharyngeal endoderm, but not in skeletogenic neural crest. Long before chondrogenesis, suc/et-1 mutant embryos have severe defects in ventral arch neural crest expression of dHAND, dlx2, msxE, gsc, dlx3 and EphA3 in the anterior arches. Dorsal expression patterns are unaffected. Later in development, suc/et-1 mutant embryos display defects in mesodermal and endodermal tissues of the pharynx. Ventral premyogenic condensations fail to express myoD, which correlates with a ventral muscle defect. Further, expression of shh in endoderm of the first pharyngeal pouch fails to extend as far laterally as in wild types. We use mosaic analyses to show that suc/et-1 functions nonautonomously in neural crest cells, and is thus required in the environment of postmigratory neural crest cells to specify ventral arch fates. Our mosaic analyses further show that suc/et-1 nonautonomously functions in mesendoderm for ventral arch muscle formation. Collectively our results support a model for dorsoventral patterning of the gnathostome pharyngeal arches in which Et-1 in the environment of the postmigratory cranial neural crest specifies the lower jaw and other ventral arch fates.


2018 ◽  
Vol 5 (7) ◽  
pp. 171463 ◽  
Author(s):  
Yunpeng Cao ◽  
Shumei Li ◽  
Yahui Han ◽  
Dandan Meng ◽  
Chunyan Jiao ◽  
...  

In plants, plant fructokinases (FRKs) are considered to be the main gateway of fructose metabolism as they can phosphorylate fructose to fructose-6-phosphate. Chinese white pears ( Pyrus bretschneideri ) are one of the popular fruits in the world market; sugar content is an important factor affecting the quality of the fruit. We identified 49 FRKs from four Rosaceae species; 20 of these sequences were from Chinese white pear. Subsequently, phylogenic relationship, gene structure and micro-collinearity were analysed. Phylogenetic and exon–intron analysis classified these FRK s into 10 subfamilies, and it was aimed to further reveal the variation of the gene structure and the evolutionary relationship of this gene family. Remarkably, gene expression patterns in different tissues or different development stages of the pear fruit suggested functional redundancy for PbFRKs derived from segmental duplication or genome-wide duplication and sub-functionalization for some of them. Additionally, PbFRK11 , PbFRK13 and PbFRK16 were found to play important roles in regulating the sugar content in the fruit. Overall, this study provided important insights into the evolution of the FRK gene family in four Rosaceae species, and highlighted its roles in both pear tissue and fruits. Results presented here provide the appropriate candidate of PbFRK s that might contribute to fructose efflux in the pear fruit.


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