scholarly journals Molecular Evolution of APP family proteins: Rapid Evolution of the Mammalian APLP1 as a Synaptic Adhesion Molecule

Author(s):  
Wataru Onodera ◽  
Toru Asahi ◽  
Naoya Sawamura

Abstract Amyloid precursor protein (APP) family members are involved in essential neuronal activities, and dysfunction of APP family members leads to neurodegenerative diseases such as Alzheimer’s disease. Among the APP gene family members, amyloid precursor-like protein 1 (APLP1) is selectively expressed in neurons and has specialized functions during synaptogenesis. Although a potential role for APLP1 in neuronal evolution has been indicated, its precise evolutionary and functional contributions are unknown. This study shows the molecular evolution of the vertebrate APP family based on phylogenetic analysis, while contrasting the evolutionary differences within the APP family. Phylogenetic analysis showed 15 times higher substitution rate that is driven by positive selection at the stem branch of the mammalian APLP1, resulting in dissimilar protein sequences compared to APP/APLP2. Docking simulation identified one positively selected site in APLP1 that alters the heparin-binding site, which could affect its function, and dimerization rate. Furthermore, the evolutionary rate covariation between the mammalian APP family and synaptic adhesion molecules (SAMs) was confirmed, indicating that only APLP1 has evolved to gain synaptic adhesion property. Overall, our results suggest that the enhanced synaptogenesis property of APLP1 as one of the SAMs may have played a role in mammalian brain evolution.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wataru Onodera ◽  
Toru Asahi ◽  
Naoya Sawamura

AbstractAmyloid precursor protein (APP) family members are involved in essential neuronal development including neurite outgrowth, neuronal migration and maturation of synapse and neuromuscular junction. Among the APP gene family members, amyloid precursor-like protein 1 (APLP1) is selectively expressed in neurons and has specialized functions during synaptogenesis. Although a potential role for APLP1 in neuronal evolution has been indicated, its precise evolutionary and functional contributions are unknown. This study shows the molecular evolution of the vertebrate APP family based on phylogenetic analysis, while contrasting the evolutionary differences within the APP family. Phylogenetic analysis showed 15 times higher substitution rate that is driven by positive selection at the stem branch of the mammalian APLP1, resulting in dissimilar protein sequences compared to APP/APLP2. Docking simulation identified one positively selected site in APLP1 that alters the heparin-binding site, which could affect its function, and dimerization rate. Furthermore, the evolutionary rate covariation between the mammalian APP family and synaptic adhesion molecules (SAMs) was confirmed, indicating that only APLP1 has evolved to gain synaptic adhesion property. Overall, our results suggest that the enhanced synaptogenesis property of APLP1 as one of the SAMs may have played a role in mammalian brain evolution.


2007 ◽  
Vol 3 (3) ◽  
pp. 209-220 ◽  
Author(s):  
Adan Aguirre ◽  
Vittorio Gallo

AbstractNeural progenitor cells that express the NG2 proteoglycan are present in different regions of the adult mammalian brain where they display distinct morphologies and proliferative rates. In the developing postnatal and adult mouse, NG2+ cells represent a major cell population of the subventricular zone (SVZ). NG2+ cells divide in the anterior and lateral region of the SVZ, and are stimulated to proliferate and migrate out of the SVZ by focal demyelination of the corpus callosum (CC). Many NG2+ cells are labeled by GFP-retrovirus injection into the adult SVZ, demonstrating that NG2+ cells actively proliferate under physiological conditions and after demyelination. Under normal physiological conditions and after focal demyelination, proliferation of NG2+ cells is significantly attenuated in wa2 mice, which are characterized by reduced signaling of the epidermal growth factor receptor (EGFR). This results in reduced SVZ-to-lesion migration of NG2+ cells and oligodendrogenesis in the lesion. Expression of vascular endothelial growth factor (VEGF) and EGFR ligands, such as heparin binding-EGF and transforming growth factor α, is upregulated in the SVZ after focal demyelination of the CC. EGF-induced oligodendrogenesis and myelin protein expression in wild-type SVZ cells in culture are significantly attenuated in wa2 SVZ cells. Our results demonstrate that the response of NG2+ cells in the SVZ and their subsequent differentiation in CC after focal demyelination depend on EGFR signaling.


2009 ◽  
Vol 9 (1) ◽  
pp. 81 ◽  
Author(s):  
Sergio Jiménez ◽  
Amy L Lawton-Rauh ◽  
Gregory L Reighard ◽  
Albert G Abbott ◽  
Douglas G Bielenberg

2021 ◽  
Vol 9 (9) ◽  
pp. 1-116
Author(s):  
Esther MF van Sluijs ◽  
Helen E Brown ◽  
Emma Coombes ◽  
Claire Hughes ◽  
Andrew P Jones ◽  
...  

Background Family-based physical activity promotion presents a promising avenue for promoting whole-family physical activity, but high-quality research is lacking. Objectives To assess the feasibility, acceptability and preliminary effectiveness of FRESH (Families Reporting Every Step to Health), a child-led online family-based physical activity intervention; and to identify effective and resource-efficient family recruitment strategies. Design The project consisted of (1) a randomised feasibility trial, (2) a randomised controlled pilot trial and (3) a systematic review and Delphi study. Setting Norfolk/Suffolk counties, UK. Participants Families, recruited from schools, workplaces and community settings, were eligible to participate if one child aged 7–11 years and one adult responsible for their care provided written consent; all family members could participate. Interventions The FRESH intervention, guided by self-determination theory, targeted whole families and was delivered via an online platform. All family members received pedometers and were given website access to select family step challenges to ‘travel’ to target cities around the world, log steps, and track progress as they virtually globetrotted. Families were randomised to FRESH intervention, pedometer-only or control arm. Main outcome measures Physical (e.g. blood pressure), psychosocial (e.g. family functioning) and behavioural (e.g. device-measured family physical activity) measures were collected at baseline and at 8- and 52-week follow-up. A mixed-methods process evaluation assessed the acceptability of the intervention and evaluation. Data sources review Systematic search of four databases (Cochrane Library, PubMed, PsycINFO and SCOPUS). Review methods Articles were screened in duplicate, and data extraction was fully checked. Academic experts participated in the three-round Delphi study. Data were combined to identify effective and resource-efficient family recruitment strategies. Inclusion criteria Included generally healthy school-aged children and at least one adult; intervention attempted to change physical activity, sedentary behaviour, screen use, diet, or prevent overweight/obesity in multiple family members; presented relevant measure of effect in children and adults. Results The feasibility study (12 families, 32 participants; 100% retention at 8 weeks) demonstrated the feasibility and acceptability of FRESH, but highlighted that adaptations were required. Of 41 families recruited in the pilot study (149 participants), 98% and 88% were retained at the 8-week and 52-week follow-up, respectively. More children in the FRESH arm self-reported doing more family physical activity, and they thought that FRESH was fun. There were no notable between-group differences in children’s outcomes. Change in moderate to vigorous physical activity at 8 weeks favoured FRESH intervention adults [vs. control: 9.4 minutes/week (95% confidence interval 0.4 to 18.4) vs. pedometer only: 15.3 (95% confidence interval 6.0 to 24.5)], and was stronger in fathers, but this was not maintained. In 49 included studies, apart from recruitment settings and strategies used (reported in 84% and 73% of the studies, respectively), recruitment details were scarce. School-based recruitment was predominant. The Delphi study identified a wide range of recruitment settings and strategies. Limitations Recruitment was the main limitation of the FRESH studies; generalisability of the proposed recruitment strategies may be limited. Conclusions This study has demonstrated the feasibility and acceptability of the FRESH intervention. However, we failed to recruit the target sample size and were unable to demonstrate a signal of effectiveness. Future research should employ a multifaceted recruitment approach. Future work Further refinements to intervention delivery and recruitment methods should be investigated. Study registration Current Controlled Trials ISRCTN12789422 and PROSPERO CRD42019140042. Funding This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 9, No. 9. See the NIHR Journals Library website for further project information.


2021 ◽  
Vol 6 (01) ◽  
pp. 74-82
Author(s):  
Tomi Apra Santosa ◽  
Winda Ayu Fietri ◽  
Abdul Razak ◽  
Ramadhan Sumarmin

Grouper fish (Serranidae) is a type of fish found in Indonesian waters. However, not many people have conducted further research on phylogenetics based on COI (Cytochrome Oxidase I). This study aims to explain the phylogeny of grouper fish from the Serranidae family based on COI (Cytochrome Oxidase I). This research is a literature study. The research samples were grouper fish from Lombok, Karimunjawa, Lampung, Kendari, Madura, Tanakeke, and Numfor. The research instrument was a grouper-type observation sheet and an observation sheet for the results of the MEGA 7 application test. The data were analyzed using qualitative descriptive analysis. The results showed that the level of kinship between the species tested was very close, including Epinephelus areolatus, E. merra, E. fasciatus, E. longispinis, E. coioides, E. ongus, and E. coeruleopunctatus with all genetic distance averages type. 0.02. The conclusion of this study is that in general the species relationships found are several species found in the same location with similar morphology and diet.


2000 ◽  
Vol 81 (12) ◽  
pp. 2833-2841 ◽  
Author(s):  
Kari Asikainen ◽  
Jukka Niemimaa ◽  
Juha Laakkonen ◽  
Tarja Hänninen ◽  
Heikki Henttonen ◽  
...  

Brain ◽  
2021 ◽  
Author(s):  
Dana Marafi ◽  
Jawid M Fatih ◽  
Rauan Kaiyrzhanov ◽  
Matteo P Ferla ◽  
Charul Gijavanekar ◽  
...  

Abstract The solute carrier (SLC) superfamily encompasses >400 transmembrane transporters involved in the exchange of amino acids, nutrients, ions, metals, neurotransmitters and metabolites across biological membranes. SLCs are highly expressed in the mammalian brain; defects in nearly 100 unique SLC-encoding genes (OMIM: https://www.omim.org) are associated with rare Mendelian disorders including developmental and epileptic encephalopathy (DEE) and severe neurodevelopmental disorders (NDDs). Exome sequencing and family-based rare variant analyses on a cohort with NDD identified two siblings with DEE and a shared deleterious homozygous splicing variant in SLC38A3. The gene encodes SNAT3, a sodium-coupled neutral amino acid transporter and a principal transporter of the amino acids asparagine, histidine, and glutamine, the latter being the precursor for the neurotransmitters GABA and glutamate. Additional subjects with a similar DEE phenotype and biallelic predicted-damaging SLC38A3 variants were ascertained through GeneMatcher and collaborations with research and clinical molecular diagnostic laboratories. Untargeted metabolomic analysis was performed to identify novel metabolic biomarkers. Ten individuals from seven unrelated families from six different countries with deleterious biallelic variants in SLC38A3 were identified. Global developmental delay, intellectual disability, hypotonia, and absent speech were common features while microcephaly, epilepsy, and visual impairment were present in the majority. Epilepsy was drug-resistant in half. Metabolomic analysis revealed perturbations of glutamate, histidine, and nitrogen metabolism in plasma, urine, and cerebrospinal fluid of selected subjects, potentially representing biomarkers of disease. Our data support the contention that SLC38A3 is a novel disease gene for DEE and illuminate the likely pathophysiology of the disease as perturbations in glutamine homeostasis.


2002 ◽  
Vol 115 (13) ◽  
pp. 2619-2622 ◽  
Author(s):  
Holly V. Goodson ◽  
William F. Hawse

Members of the actin family have well-characterized cytoskeletal functions,but actin and actin-related proteins (ARPs) have also been implicated in nuclear activities. Previous analyses of the actin family have identified four conserved subfamilies, but many actin-related proteins (ARPs) do not fall into these groups. A new systematic phylogenetic analysis reveals that at least eight ARP subfamilies are conserved from humans to yeast, indicating that these ARPs are part of the core set of eukaryotic proteins. Members of at least three subfamilies appear to be involved in chromatin remodeling,suggesting that ARPs play ancient, fundamental roles in this nuclear process.


2020 ◽  
Vol 117 (19) ◽  
pp. 10554-10564 ◽  
Author(s):  
Annalisa Paolino ◽  
Laura R. Fenlon ◽  
Peter Kozulin ◽  
Elizabeth Haines ◽  
Jonathan W. C. Lim ◽  
...  

A unique combination of transcription factor expression and projection neuron identity demarcates each layer of the cerebral cortex. During mouse and human cortical development, the transcription factor CTIP2 specifies neurons that project subcerebrally, while SATB2 specifies neuronal projections via the corpus callosum, a large axon tract connecting the two neocortical hemispheres that emerged exclusively in eutherian mammals. Marsupials comprise the sister taxon of eutherians but do not have a corpus callosum; their intercortical commissural neurons instead project via the anterior commissure, similar to egg-laying monotreme mammals. It remains unknown whether divergent transcriptional networks underlie these cortical wiring differences. Here, we combine birth-dating analysis, retrograde tracing, gene overexpression and knockdown, and axonal quantification to compare the functions of CTIP2 and SATB2 in neocortical development, between the eutherian mouse and the marsupial fat-tailed dunnart. We demonstrate a striking degree of structural and functional homology, whereby CTIP2 or SATB2 of either species is sufficient to promote a subcerebral or commissural fate, respectively. Remarkably, we reveal a substantial delay in the onset of developmental SATB2 expression in mice as compared to the equivalent stage in dunnarts, with premature SATB2 overexpression in mice to match that of dunnarts resulting in a marsupial-like projection fate via the anterior commissure. Our results suggest that small alterations in the timing of regulatory gene expression may underlie interspecies differences in neuronal projection fate specification.


PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49771 ◽  
Author(s):  
Vijayakumar Gosu ◽  
Shaherin Basith ◽  
Prasannavenkatesh Durai ◽  
Sangdun Choi

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