FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2411643890> ?p ?o ?g. }

• W2411643890 abstract "Background Genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID). Recently, we reported on 23 individuals in 17 families with loss CNVs or frame-shifting indels disrupting PTCHD1. However, little is known for the function of PTCHD1. Objectives PTCHD1 , an X-linked gene for ASD and/or (ID), encodes a protein with homology to the sonic hedgehog (Shh) receptors PTCH1 and 2, and has been reported to show similar Gli repression activity. However, little else is known about the function of PTCHD1 or the pathway (s) that are perturbed by PTCHD1 mutations leading to ASD/ID. Design/method We looked at the effect of over-expression of PTCHD1 on transcription levels of neuronal and synapse-related genes. We also included a truncated construct lacking the C-terminal four amino acids, Ile-Thr-Thr-Val (ITTV) of PTCHD1 , which is predicted to interact with the PDZ domains of proteins. We tested the transcription of Shh and its putative receptor, Ptchd1 , and Smoothened (Smo) , from mouse embryonic and postnatal brains. We also analysed the expression of PTCHD1 and Smo in primary cilia. Results Transcriptional analysis showed Shh, Ptch1, and Smo expressed in developing mouse embryonic and postnatal hippocampus, but with gradually decreasing levels, whereas Ptchd1 levels steadily increase, suggesting that Ptchd1 may be more relevant in later embryonic and postnatal neurodevelopment. Preliminary results indicate that PTCHD1 is able to localise to the cilia. A significant increase in level of transcription of NLGN1 and CNTNAP1 that is dependent on the C-terminal four amino acids of PTCHD1 suggests either a regulatory or a downstream effect of PTCHD1 on these genes via a PDZ-domain containing protein. Positive PTCHD1 immunolabeling was visible in the hippocampal neurons. Preliminary results also suggest localization of PTCHD1 in cilia. Conclusions We report here a potential role for the PDZ binding domain in PTCHD1 in regulating expression of Nlgn1 and Cntnap1. PDZ domains are found in many eukaryotic and bacterial proteins, and in particular many proteins that are important for synaptic functioning. We speculate that PTCHD1 localization to primary cilia in hippocampal neurons could inhibit the Hh pathway by excluding SMO, allowing cilia to function as Shh sensors, in a manner similar to that of PTCH1, during neurodevelopment. The PTCHD1 gene has a role in a neurobiological pathway that delivers information to cells during brain development and CNVs and mutations may disrupt crucial developmental processes, contributing to the onset of autism." @default.
• W2411643890 created "2016-06-24" @default.
• W2411643890 creator A5011233568 @default.
• W2411643890 creator A5027716038 @default.
• W2411643890 creator A5036637906 @default.
• W2411643890 creator A5059028708 @default.
• W2411643890 date "2015-11-01" @default.
• W2411643890 modified "2023-09-27" @default.
• W2411643890 title "MG-136 Functional analysis of the autism and intellectual disability gene PTCHD1 reveals hedgehog receptor-like functions and pdz-binding domain-specific regulation of CNTNAP1 and NLGN1" @default.
• W2411643890 doi "https://doi.org/10.1136/jmedgenet-2015-103578.35" @default.
• W2411643890 hasPublicationYear "2015" @default.
• W2411643890 type Work @default.
• W2411643890 sameAs 2411643890 @default.
• W2411643890 citedByCount "0" @default.
• W2411643890 crossrefType "journal-article" @default.
• W2411643890 hasAuthorship W2411643890A5011233568 @default.
• W2411643890 hasAuthorship W2411643890A5027716038 @default.
• W2411643890 hasAuthorship W2411643890A5036637906 @default.
• W2411643890 hasAuthorship W2411643890A5059028708 @default.
• W2411643890 hasConcept C104317684 @default.
• W2411643890 hasConcept C145837895 @default.
• W2411643890 hasConcept C2776637008 @default.
• W2411643890 hasConcept C2778539099 @default.
• W2411643890 hasConcept C2779477247 @default.
• W2411643890 hasConcept C54355233 @default.
• W2411643890 hasConcept C86339819 @default.
• W2411643890 hasConcept C86803240 @default.
• W2411643890 hasConcept C88498014 @default.
• W2411643890 hasConceptScore W2411643890C104317684 @default.
• W2411643890 hasConceptScore W2411643890C145837895 @default.
• W2411643890 hasConceptScore W2411643890C2776637008 @default.
• W2411643890 hasConceptScore W2411643890C2778539099 @default.
• W2411643890 hasConceptScore W2411643890C2779477247 @default.
• W2411643890 hasConceptScore W2411643890C54355233 @default.
• W2411643890 hasConceptScore W2411643890C86339819 @default.
• W2411643890 hasConceptScore W2411643890C86803240 @default.
• W2411643890 hasConceptScore W2411643890C88498014 @default.
• W2411643890 hasLocation W24116438901 @default.
• W2411643890 hasOpenAccess W2411643890 @default.
• W2411643890 hasPrimaryLocation W24116438901 @default.
• W2411643890 hasRelatedWork W1834036377 @default.
• W2411643890 hasRelatedWork W1967297293 @default.
• W2411643890 hasRelatedWork W1975911274 @default.
• W2411643890 hasRelatedWork W1981936732 @default.
• W2411643890 hasRelatedWork W2007330654 @default.
• W2411643890 hasRelatedWork W2067482101 @default.
• W2411643890 hasRelatedWork W2112471545 @default.
• W2411643890 hasRelatedWork W2137958315 @default.
• W2411643890 hasRelatedWork W2173629501 @default.
• W2411643890 hasRelatedWork W2794389439 @default.
• W2411643890 hasRelatedWork W2887478137 @default.
• W2411643890 hasRelatedWork W2942878014 @default.
• W2411643890 hasRelatedWork W2948496992 @default.
• W2411643890 hasRelatedWork W2974261743 @default.
• W2411643890 hasRelatedWork W2996696612 @default.
• W2411643890 hasRelatedWork W3014982882 @default.
• W2411643890 hasRelatedWork W3048857987 @default.
• W2411643890 hasRelatedWork W3092290783 @default.
• W2411643890 hasRelatedWork W3120149338 @default.
• W2411643890 hasRelatedWork W3144289922 @default.
• W2411643890 isParatext "false" @default.
• W2411643890 isRetracted "false" @default.
• W2411643890 magId "2411643890" @default.
• W2411643890 workType "article" @default.