Ups and downs of lysosomal pH: conflicting roles of LAMP proteins?
Autophagy. 2023 Nov 14:1-4. doi: 10.1080/15548627.2023.2274253. Online ahead of print.ABSTRACTThe acidic pH of lysosomes is critical for catabolism in eukaryotic cells and is altered in neurodegenerative disease including Alzheimer and Parkinson. Recent reports using Drosophila and mammalian cell culture systems have identified novel and, at first sight, conflicting roles for the lysosomal associated membrane proteins (LAMPs) in the regulation of the endolysosomal system.Abbreviation: AD: Alzheimer disease; LAMP: lysosomal associated membrane protein; LTR: LysoTracker; PD: Parkinson disease; TMEM175: transmembrane protein ...
Source: Autophagy - November 14, 2023 Category: Cytology Authors: Jonathan Handy Gustavo C Macintosh Andreas Jenny Source Type: research
< em > Pycard < /em > deficiency inhibits microRNA maturation and prevents neointima formation by promoting chaperone-mediated autophagic degradation of AGO2/argonaute 2 in adipose tissue
Autophagy. 2023 Nov 14:1-16. doi: 10.1080/15548627.2023.2277610. Online ahead of print.ABSTRACTPYCARD (PYD and CARD domain containing), a pivotal adaptor protein in inflammasome assembly and activation, contributes to innate immunity, and plays an essential role in the pathogenesis of atherosclerosis and restenosis. However, its roles in microRNA biogenesis remain unknown. Therefore, this study aimed to investigate the roles of PYCARD in miRNA biogenesis and neointima formation using pycard knockout (pycard-/-) mice. Deficiency of Pycard reduced circulating miRNA profile and inhibited Mir17 seed family maturation. The syst...
Source: Autophagy - November 14, 2023 Category: Cytology Authors: Jian Li Hongmin Yao Fujie Zhao Junqing An Qilong Wang Jing Mu Zhixue Liu Ming-Hui Zou Zhonglin Xie Source Type: research
Ups and downs of lysosomal pH: conflicting roles of LAMP proteins?
Autophagy. 2023 Nov 14:1-4. doi: 10.1080/15548627.2023.2274253. Online ahead of print.ABSTRACTThe acidic pH of lysosomes is critical for catabolism in eukaryotic cells and is altered in neurodegenerative disease including Alzheimer and Parkinson. Recent reports using Drosophila and mammalian cell culture systems have identified novel and, at first sight, conflicting roles for the lysosomal associated membrane proteins (LAMPs) in the regulation of the endolysosomal system.Abbreviation: AD: Alzheimer disease; LAMP: lysosomal associated membrane protein; LTR: LysoTracker; PD: Parkinson disease; TMEM175: transmembrane protein ...
Source: Autophagy - November 14, 2023 Category: Cytology Authors: Jonathan Handy Gustavo C Macintosh Andreas Jenny Source Type: research
NCoR1: a key player regulating mycobacterium tuberculosis pathogenesis
Autophagy. 2023 Nov 12:1-2. doi: 10.1080/15548627.2023.2277583. Online ahead of print.ABSTRACTMycobacterium tuberculosis (Mtb) employs a multifaceted arsenal to elude host defense mechanisms, including those associated with autophagy and lysosome function. Within the realm of host-pathogen interactions, NCOR1, a well-recognized transcriptional co-repressor, is known to associate with a multitude of protein complexes to effect the repression of a diverse spectrum of genes. However, its role in regulating macroautophagy/autophagy, lysosome biogenesis, and, by extension, Mtb pathogenesis remains unexplored. The depletion of N...
Source: Autophagy - November 13, 2023 Category: Cytology Authors: Kaushik Sen Viplov Kumar Biswas Arup Ghosh Subhasish Prusty Sourya Prakash Nayak Sreeparna Podder Bhawna Gupta Sunil Kumar Raghav Source Type: research
Connecting reticulophagy and neuronal NTRK2/TrkB signaling
Autophagy. 2023 Nov 8:1-2. doi: 10.1080/15548627.2023.2276630. Online ahead of print.ABSTRACTTightly regulated cell surface expression of NTRK2/TrkB provides a mechanism for fine-tuning cellular responses to the neurotrophic factor BDNF. Recently, the degradation of NTRK2 by reticulophagy has been identified as a mechanism to limit its availability for trafficking to the cell membrane. The ER-chaperone CANX (calnexin) delivers NTRK2 to the reticulophagy receptor RETREG1/Fam134b for lysosomal degradation. Upon phosphorylation of CANX, NTRK2 is released from this complex, which facilitates its cell surface transport. These r...
Source: Autophagy - November 9, 2023 Category: Cytology Authors: Patrick L üningschrör Michael Sendtner Source Type: research
A conserved requirement for RME-8/DNAJC13 in neuronal autophagic lysosome reformation
We report new analysis of the requirements for the RME-8/DNAJC13 protein in neurons, focusing on intact C. elegans mechanosensory neurons, and primary mouse cortical neurons in culture. Loss of RME-8/DNAJC13 in both systems results in accumulation of grossly elongated autolysosomal tubules. Further C. elegans analysis revealed a similar autolysosome tubule accumulation defect in mutants known to be required for ALR in mammals, including mutants lacking bec-1/BECN1/Beclin1 and vps-15/PIK3R4/p150 that regulate the class III phosphatidylinositol 3-kinase (PtdIns3K) VPS-34, and dyn-1/dynamin that severs ALR tubules. Clathrin i...
Source: Autophagy - November 9, 2023 Category: Cytology Authors: Sierra B Swords Nuo Jia Anne Norris Jil Modi Qian Cai Barth D Grant Source Type: research
Connecting reticulophagy and neuronal NTRK2/TrkB signaling
Autophagy. 2023 Nov 8:1-2. doi: 10.1080/15548627.2023.2276630. Online ahead of print.ABSTRACTTightly regulated cell surface expression of NTRK2/TrkB provides a mechanism for fine-tuning cellular responses to the neurotrophic factor BDNF. Recently, the degradation of NTRK2 by reticulophagy has been identified as a mechanism to limit its availability for trafficking to the cell membrane. The ER-chaperone CANX (calnexin) delivers NTRK2 to the reticulophagy receptor RETREG1/Fam134b for lysosomal degradation. Upon phosphorylation of CANX, NTRK2 is released from this complex, which facilitates its cell surface transport. These r...
Source: Autophagy - November 9, 2023 Category: Cytology Authors: Patrick L üningschrör Michael Sendtner Source Type: research
A conserved requirement for RME-8/DNAJC13 in neuronal autophagic lysosome reformation
We report new analysis of the requirements for the RME-8/DNAJC13 protein in neurons, focusing on intact C. elegans mechanosensory neurons, and primary mouse cortical neurons in culture. Loss of RME-8/DNAJC13 in both systems results in accumulation of grossly elongated autolysosomal tubules. Further C. elegans analysis revealed a similar autolysosome tubule accumulation defect in mutants known to be required for ALR in mammals, including mutants lacking bec-1/BECN1/Beclin1 and vps-15/PIK3R4/p150 that regulate the class III phosphatidylinositol 3-kinase (PtdIns3K) VPS-34, and dyn-1/dynamin that severs ALR tubules. Clathrin i...
Source: Autophagy - November 9, 2023 Category: Cytology Authors: Sierra B Swords Nuo Jia Anne Norris Jil Modi Qian Cai Barth D Grant Source Type: research
Connecting reticulophagy and neuronal NTRK2/TrkB signaling
Autophagy. 2023 Nov 8:1-2. doi: 10.1080/15548627.2023.2276630. Online ahead of print.ABSTRACTTightly regulated cell surface expression of NTRK2/TrkB provides a mechanism for fine-tuning cellular responses to the neurotrophic factor BDNF. Recently, the degradation of NTRK2 by reticulophagy has been identified as a mechanism to limit its availability for trafficking to the cell membrane. The ER-chaperone CANX (calnexin) delivers NTRK2 to the reticulophagy receptor RETREG1/Fam134b for lysosomal degradation. Upon phosphorylation of CANX, NTRK2 is released from this complex, which facilitates its cell surface transport. These r...
Source: Autophagy - November 9, 2023 Category: Cytology Authors: Patrick L üningschrör Michael Sendtner Source Type: research
A conserved requirement for RME-8/DNAJC13 in neuronal autophagic lysosome reformation
We report new analysis of the requirements for the RME-8/DNAJC13 protein in neurons, focusing on intact C. elegans mechanosensory neurons, and primary mouse cortical neurons in culture. Loss of RME-8/DNAJC13 in both systems results in accumulation of grossly elongated autolysosomal tubules. Further C. elegans analysis revealed a similar autolysosome tubule accumulation defect in mutants known to be required for ALR in mammals, including mutants lacking bec-1/BECN1/Beclin1 and vps-15/PIK3R4/p150 that regulate the class III phosphatidylinositol 3-kinase (PtdIns3K) VPS-34, and dyn-1/dynamin that severs ALR tubules. Clathrin i...
Source: Autophagy - November 9, 2023 Category: Cytology Authors: Sierra B Swords Nuo Jia Anne Norris Jil Modi Qian Cai Barth D Grant Source Type: research
Connecting reticulophagy and neuronal NTRK2/TrkB signaling
Autophagy. 2023 Nov 8:1-2. doi: 10.1080/15548627.2023.2276630. Online ahead of print.ABSTRACTTightly regulated cell surface expression of NTRK2/TrkB provides a mechanism for fine-tuning cellular responses to the neurotrophic factor BDNF. Recently, the degradation of NTRK2 by reticulophagy has been identified as a mechanism to limit its availability for trafficking to the cell membrane. The ER-chaperone CANX (calnexin) delivers NTRK2 to the reticulophagy receptor RETREG1/Fam134b for lysosomal degradation. Upon phosphorylation of CANX, NTRK2 is released from this complex, which facilitates its cell surface transport. These r...
Source: Autophagy - November 9, 2023 Category: Cytology Authors: Patrick L üningschrör Michael Sendtner Source Type: research
A conserved requirement for RME-8/DNAJC13 in neuronal autophagic lysosome reformation
We report new analysis of the requirements for the RME-8/DNAJC13 protein in neurons, focusing on intact C. elegans mechanosensory neurons, and primary mouse cortical neurons in culture. Loss of RME-8/DNAJC13 in both systems results in accumulation of grossly elongated autolysosomal tubules. Further C. elegans analysis revealed a similar autolysosome tubule accumulation defect in mutants known to be required for ALR in mammals, including mutants lacking bec-1/BECN1/Beclin1 and vps-15/PIK3R4/p150 that regulate the class III phosphatidylinositol 3-kinase (PtdIns3K) VPS-34, and dyn-1/dynamin that severs ALR tubules. Clathrin i...
Source: Autophagy - November 9, 2023 Category: Cytology Authors: Sierra B Swords Nuo Jia Anne Norris Jil Modi Qian Cai Barth D Grant Source Type: research
MAP4K2 connects the Hippo pathway to autophagy in response to energy stress
Autophagy. 2023 Nov 8. doi: 10.1080/15548627.2023.2280876. Online ahead of print.ABSTRACTAs a key regulator of development, organ size, tissue homeostasis and cancer, the Hippo pathway is tightly regulated by various growth-related signaling events. Among them, energy stress activates the Hippo pathway to inhibit its downstream effector YAP1. Our recent work reported a YAP1-independent role of the Hippo pathway in promoting macroautophagy/autophagy and cell survival in response to energy stress, a process mediated by Hippo kinase MAP4K2. MAP4K2 interacts with and phosphorylates MAP1LC3A/LC3A at S87, which in turn drives au...
Source: Autophagy - November 8, 2023 Category: Cytology Authors: Gayoung Seo Joshua Mckinley Wenqi Wang Source Type: research
ATG9B is a tissue-specific homotrimeric lipid scramblase that can compensate for ATG9A
Autophagy. 2023 Nov 8. doi: 10.1080/15548627.2023.2275905. Online ahead of print.ABSTRACTMacroautophagy/autophagy is a fundamental aspect of eukaryotic biology, and the autophagy-related protein ATG9A is part of the core machinery facilitating this process. In addition to ATG9A vertebrates encode ATG9B, a poorly characterized paralog expressed in a subset of tissues. Herein, we characterize the structure of human ATG9B revealing the conserved homotrimeric quaternary structure and explore the conformational dynamics of the protein. Consistent with the experimental structure and computational chemistry, we establish that ATG...
Source: Autophagy - November 8, 2023 Category: Cytology Authors: George N Chiduza Acely Garza-Garcia Eugenia Almacellas Stefano De Tito Valerie E Pye Alexander R van Vliet Peter Cherepanov Sharon A Tooze Source Type: research
CSNK2 suppresses autophagy by activating FLN-NHL-containing TRIM proteins
Autophagy. 2023 Nov 8. doi: 10.1080/15548627.2023.2281128. Online ahead of print.ABSTRACTMacroautophagy/autophagy is a tightly regulated cellular process integral to homeostasis and innate immunity. As such, dysregulation of autophagy is associated with cancer, neurodegenerative disorders, and infectious diseases. While numerous factors that promote autophagy have been characterized, the key mechanisms that prevent excessive autophagy are less well understood. Here, we identify CSNK2/CK2 (casein kinase 2) as a negative regulator of autophagy. Pharmacological inhibition of CSNK2 activity or siRNA-mediated depletion of CSNK2...
Source: Autophagy - November 8, 2023 Category: Cytology Authors: Helene Hoenigsperger Lennart Koepke Dhiraj Acharya Victoria Hunszinger Dennis Freisem Alexander Grenzner Sebastian Wiese Frank Kirchhoff Michaela U Gack Konstantin M J Sparrer Source Type: research
