Genomic organization and alternative splicing of the human and mouse RPTPρ genes

BACKGROUND: Receptor protein tyrosine phosphatase rho (RPTPρ, gene symbol PTPRT) is a member of the type IIB RPTP family. These transmembrane molecules have been linked to signal transduction, cell adhesion and neurite extension. The extracellular segment contains MAM, Ig-like and fibronectin type III domains, and the intracellular segment contains two phosphatase domains. The human RPTPρ gene is located on chromosome 20q12-13.1, and the mouse gene is located on a syntenic region of chromosome 2. RPTPρ expression is restricted to the central nervous system. RESULTS: The cloning of the mouse cDNA, identification of alternatively spliced exons, detection of an 8 kb 3'-UTR, and the genomic organization of human and mouse RPTPρ genes are described. The two genes are comprised of at least 33 exons. Both RPTPρ genes span over 1 Mbp and are the largest RPTP genes characterized. Exons encoding the extracellular segment through the intracellular juxtamembrane 'wedge' region are widely spaced, with introns ranging from 9.7 to 303.7 kb. In contrast, exons encoding the two phosphatase domains are more tightly clustered, with 15 exons spanning ∼ 60 kb, and introns ranging in size from 0.6 kb to 13.1 kb. Phase 0 introns predominate in the intracellular, and phase 1 in the extracellular segment. CONCLUSIONS: We report the first genomic characterization of a RPTP type IIB gene. Alternatively spliced variants may result in different RPTPρ isoforms. Our findings suggest that RPTPρ extracellular and intracellular segments originated as separate modular proteins that fused into a single transmembrane molecule during a later evolutionary period

Introducing Gamification for Advancing Current Mental Healthcare and Treatment Practices

Given the alarming rise in the mental health issues among individuals of all age groups, it somehow becomes imperative to find novel solutions to deal with the existing global mental health crisis. Since affective and cognitive processes largely define our behavioral goals and tendencies, gamification has garnered immense interest among the mental health research community as a potential methodology to help modify any maladaptive perception, cognition, and behavior. Applying gaming in a therapeutic environment, undoubtedly, comes with a diverse set of advantages, which ranges from automatic tapping into the internal psychological mechanisms to increasing motivation to change, among many others. Thus, the advances in gamification elements have provided a straight revelation about the future directions of assessment, diagnosis, and treatment of various mental health conditions. With a brief introduction to the existing application of gamification in primary healthcare sectors, the present chapter will, therefore, aim to extend the scope of gamification to improve mental health issues. An extensive review of literature in this field will further educate readers about the popular domains in mental health, which currently apply gamification app technologies. This chapter will also attempt to provide empirical instances to suggest how gamification can improve the non-compliance rate to therapies as well as motivation to induce behavioral changes. The primary focus of this chapter is to enlighten its readers on how gamification using mobile and computer apps can digitally enhance and aid the present-day mental health diagnosis and treatment practices. This advancement will hopefully allow mental health experts, therapists, and psychologists to move beyond traditional psychotherapeutic interventions and diagnostic methods to a better and futuristic approach to understanding and treating clinical disorders. Furthermore, future implications and challenges will also be discussed. © 2021, The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd

Molecular analysis of receptor protein tyrosine phosphatase μ-mediated cell adhesion

Type IIB receptor protein tyrosine phosphatases (RPTPs) are bi-functional cell surface molecules. Their ectodomains mediate stable, homophilic, cell-adhesive interactions, whereas the intracellular catalytic regions can modulate the phosphorylation state of cadherin/catenin complexes. We describe a systematic investigation of the cell-adhesive properties of the extracellular region of RPTPμ, a prototypical type IIB RPTP. The crystal structure of a construct comprising its N-terminal MAM (meprin/A5/μ) and Ig domains was determined at 2.7 Å resolution; this assigns the MAM fold to the jelly-roll family and reveals extensive interactions between the two domains, which form a rigid structural unit. Structure-based site-directed mutagenesis, serial domain deletions and cell-adhesion assays allowed us to identify the four N-terminal domains (MAM, Ig, fibronectin type III (FNIII)-1 and FNIII-2) as a minimal functional unit. Biophysical characterization revealed at least two independent types of homophilic interaction which, taken together, suggest that there is the potential for formation of a complex and possibly ordered array of receptor molecules at cell contact sites