scholarly journals An Essential Role for the Tetraspanin LHFPL4 in the Cell-Type-Specific Targeting and Clustering of Synaptic GABA A Receptors

Cell Reports ◽  
2017 ◽  
Vol 21 (1) ◽  
pp. 70-83 ◽  
Author(s):  
Elizabeth C. Davenport ◽  
Valentina Pendolino ◽  
Georgina Kontou ◽  
Thomas P. McGee ◽  
David F. Sheehan ◽  
...  
Keyword(s):  
Essential Role ◽  
Cell Type ◽  
Gaba A ◽  
Specific Targeting ◽  
Cell Type Specific

scholarly journals Characterization of Cre recombinase  mouse lines enabling cell type‐specific targeting of postnatal intervertebral discs

2019 ◽  
Vol 234 (9) ◽  
pp. 14422-14431 ◽  
Author(s):  
Yixin Zheng ◽  
Xuejie Fu ◽  
Qingbai Liu ◽  
Shengqi Guan ◽  
Cunchang Liu ◽  
...  
Keyword(s):  
Cre Recombinase ◽  
Intervertebral Discs ◽  
Cell Type ◽  
Specific Targeting ◽  
Cell Type Specific ◽  
Mouse Lines

scholarly journals Cell-type Specific Targeting of the α2c-Adrenoceptor

2000 ◽  
Vol 275 (45) ◽  
pp. 35424-35431 ◽  
Author(s):  
Carl M. Hurt ◽  
Felix Y. Feng ◽  
Brian Kobilka
Keyword(s):  
Cell Type ◽  
Specific Targeting ◽  
Cell Type Specific

scholarly journals Cell-type-specific targeting of viral vectors in the mammalian brain

2018 ◽  
Vol WCP2018 (0) ◽  
pp. PO4-1-90
Author(s):  
Toshiaki Suzuki ◽  
Yuji Masaki ◽  
Taiki Hara ◽  
Nao Morimoto ◽  
Fumitaka Osakada
Keyword(s):  
Viral Vectors ◽  
Mammalian Brain ◽  
Cell Type ◽  
Specific Targeting ◽  
Cell Type Specific

scholarly journals ALS and FTD-associated missense mutations in TBK1 differentially disrupt mitophagy

2021 ◽  
Author(s):  
Olivia Harding ◽  
Chantell S Evans ◽  
Junqiang Ye ◽  
Jonah Cheung ◽  
Tom Maniatis ◽  
...  
Keyword(s):  
Essential Role ◽  
Molecular Mechanisms ◽  
Kinase Activity ◽  
Primary Neurons ◽  
Missense Mutations ◽  
Cell Type ◽  
Mitochondrial Stress ◽  
Specific Effects ◽  
Cell Type Specific ◽  
Lateral Sclerosis

TANK-binding kinase 1 (TBK1) is a multi-functional kinase with an essential role in mitophagy, the selective clearance of damaged mitochondria. More than 90 distinct mutations in TBK1 are linked to amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD), including missense mutations that disrupt the ability of TBK1 to dimerize, associate with the mitophagy receptor optineurin (OPTN), auto-activate, or catalyze phosphorylation. We investigated how ALS-associated mutations in TBK1 affect Parkin-dependent mitophagy using imaging to dissect the molecular mechanisms involved in clearing damaged mitochondria. Some mutations cause severe dysregulation of the pathway, while others induce limited disruption. Mutations that abolish either TBK1 dimerization or kinase activity were insufficient to fully inhibit mitophagy, while mutations that reduced both dimerization and kinase activity were more disruptive. Ultimately, both TBK1 recruitment and OPTN phosphorylation at S177 are necessary for engulfment of damaged mitochondra by autophagosomal membranes. Surprisingly, we find that ULK1 activity contributes to the phosphorylation of OPTN in the presense of either WT- or kinase inactive TBK1. In primary neurons, TBK1 mutants induce mitochondrial stress under basal conditions; network stress is exacerbated with further mitochondrial insult. Our study further refines the model for TBK1 function in mitophagy, demonstrating that some ALS-linked mutations likely contribute to disease pathogenesis by inducing mitochondrial stress or inhibiting mitophagic flux. Other TBK1 mutations exhibited much less impact on mitophagy in our assays, suggesting that cell-type specific effects, cumulative damage, or alternative TBK1-dependent pathways such as innate immunity and inflammation also factor into the development of ALS in affected individuals.

scholarly journals MHC I–associated peptides preferentially derive from transcripts bearing miRNA response elements

Blood ◽  
2012 ◽  
Vol 119 (26) ◽  
pp. e181-e191 ◽  
Author(s):  
Diana Paola Granados ◽  
Wafaa Yahyaoui ◽  
Céline M. Laumont ◽  
Tariq Daouda ◽  
Tara L. Muratore-Schroeder ◽  
...  
Keyword(s):  
Cell Surface ◽  
B Lymphocytes ◽  
Essential Role ◽  
Physical Nature ◽  
Cell Type ◽  
Mhc I ◽  
Response Elements ◽  
Human B Cells ◽  
A Cell ◽  
Cell Type Specific

Abstract MHC I–associated peptides (MIPs) play an essential role in normal homeostasis and diverse pathologic conditions. MIPs derive mainly from defective ribosomal products (DRiPs), a subset of nascent proteins that fail to achieve a proper conformation and the physical nature of which remains elusive. In the present study, we used high-throughput proteomic and transcriptomic methods to unravel the structure and biogenesis of MIPs presented by HLA-A and HLA-B molecules on human EBV-infected B lymphocytes from 4 patients. We found that although HLA-different subjects present distinctive MIPs derived from different proteins, these MIPs originate from proteins that are functionally interconnected and implicated in similar biologic pathways. Secondly, the MIP repertoire of human B cells showed no bias toward conserved versus polymorphic genomic sequences, were derived preferentially from abundant transcripts, and conveyed to the cell surface a cell-type–specific signature. Finally, we discovered that MIPs derive preferentially from transcripts bearing miRNA response elements. Furthermore, whereas MIPs of HLA-disparate subjects are coded by different sets of transcripts, these transcripts are regulated by mostly similar miRNAs. Our data support an emerging model in which the generation of MIPs by a transcript depends on its abundance and DRiP rate, which is regulated to a large extent by miRNAs.

Sign in / Sign up

Export Citation Format

Share Document