Article
Cell Biology
Claudia Puri, David C. Rubinsztein
Summary: Using superresolution structured illumination microscopy and electron microscopy, researchers have found that mammalian autophagosomes derive from finger-like outgrowths from the recycling endosome. These fingers close into a fist and the openings are sealed in an ESCRT-dependent fashion. The scission of the autophago-dome liberates free autophagosomes from this compartment, revealing unexpected morphologies of autophagosome precursors and raising new questions about the control of this process.
Article
Cell Biology
Simona M. Migliano, Sebastian W. Schultz, Eva M. Wenzel, Szabolcs Takats, Dan Liu, Silje Mork, Kia Wee Tan, Tor Erik Rusten, Camilla Raiborg, Harald Stenmark
Summary: This study describes a surveillance mechanism in cells that allows the detection and clearance of abnormal endosomes with receptor accumulation and elevated signaling through an autophagic process. This process, called simaphagy, serves as a failsafe mechanism in signal termination.
Article
Biology
Sho W. Suzuki, Akihiko Oishi, Nadia Nikulin, Jeff R. Jorgensen, Matthew G. Baile, Scott D. Emr
Summary: The study uncovered a novel endosomal retrieval pathway mediated by Mvp1 protein, which deforms and cuts the endosomal membrane to release recycling tubules, distinct from traditional pathways. Additionally, human homolog SNX8, also implicated in Alzheimer's disease, participates in the formation of endosomal recycling tubules, revealing a conserved mechanism from yeast to humans.
Article
Biology
Cheng-Wen He, Xue-Fei Cui, Shao-Jie Ma, Qin Xu, Yan-Peng Ran, Wei-Zhi Chen, Jun-Xi Mu, Hui Li, Jing Zhu, Qingqiu Gong, Zhiping Xie
Summary: Our study reveals a unique vacuolar membrane protein degradation process that depends on vacuole-associated Atg8 downstream of ESCRTs. We also identify a specific role of Hfl1, a conserved protein, in membrane targeting of Atg8. These findings contribute to a better understanding of the molecular mechanisms involved in vacuole degradation processes.
Review
Cell Biology
Tiffany G. Roach, Helja K. M. Lang, Wen Xiong, Samppa J. Ryhanen, Daniel G. S. Capelluto
Summary: TOM1, a member of the ESCRT protein family, plays a role in endosomal cargo sorting and forms complexes with other ESCRT proteins. It has also been found to participate in physiological processes such as autophagy, immune responses, and neuroinflammation, as well as serve as a survival mechanism for bacterial infections and cancer progression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
A. King Cada, Mark R. Pavlin, Juan P. Castillo, Alexander B. Tong, Kevin P. Larsen, Xuefeng Ren, Adam L. Yokom, Feng-Ching Tsai, Jamie Shiah, Patricia M. Bassereau, Carlos J. Bustamante, James H. Hurley
Summary: The endosomal sorting complexes required for transport (ESCRT) system is a membrane scission machinery that catalyzes the budding and scission of membranes. In this study, researchers investigated the capability of CHMP1B and IST1, two ESCRT-III subunits, to sever membranes on their own or in concert with VPS4 or spastin. They found that CHMP1B and IST1 can form stable scaffolds on membrane nanotubes but do not lead to scission. However, when an additional extensional force was applied, the CHMP1B-IST1 scaffolded tubes were severed, suggesting a friction-driven scission mechanism. The protein spastin was found to colocalize with CHMP1B-enriched sites but did not disassemble the CHMP1B-IST1 coat from the membrane. VPS4, on the other hand, resolubilized CHMP1B and IST1 without leading to scission. These results demonstrate that CHMP1B-IST1 can sever membranes by a friction-driven mechanism independent of VPS4 and spastin.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
John W. McLean, Julie A. Wilson, Tina Tian, Jennifer A. Watson, Mary VanHart, Andrew J. Bean, Steven S. Scherer, David K. Crossman, Eroboghene Ubogu, Scott M. Wilson
Summary: Endosomal sorting is crucial for neural development by regulating membrane receptor distribution and signaling pathways. Inactivation of the HGS protein in Schwann cells leads to peripheral neuropathy with deficits in motor and sensory functions, delayed myelination, and altered gene expression related to Schwann cell maturation. This study suggests that HGS is essential for endosomal sorting of ERBB2/3 receptors during Schwann cell development, implicating endosomal dysfunction in inherited peripheral neuropathies.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Cell Biology
Yan Zhen, Harald Stenmark
Summary: Autophagy is a crucial process for cellular homeostasis, involving the degradation of cytoplasmic material through the formation of autophagosomes. Recent research has highlighted the role of vesicles containing ATG9 as potential initiators of autophagosome formation, as well as the involvement of ESCRT proteins in sealing the phagophore.
Article
Cell Biology
Pauline P. Marie, Shih-Jung Fan, John Mason, Adam Wells, Claudia C. Mendes, S. Mark Wainwright, Sheherezade Scott, Roman Fischer, Adrian L. Harris, Clive Wilson, Deborah C. I. Goberdhan
Summary: Exosomes are secreted nanovesicles formed in late endosomes with the help of core proteins of the Endosomal Sorting Complex Required for Transport (ESCRT). Accessory ESCRT-III components are involved in vesicle scission but have a specific role in Rab11a-exosome generation. Knockdown of these proteins inhibits exosome production and suppresses pro-tumorigenic activities.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Review
Biochemistry & Molecular Biology
Yasuyoshi Sakai, Masahide Oku
Summary: The discovery of microautophagy dates back to 1966, and since then research has focused on understanding its physiological significance and molecular mechanisms. Recent studies have found that ATG proteins and ESCRT proteins play important roles in microautophagy.
Article
Biology
Dmitry Shvarev, Jannis Schoppe, Caroline Koenig, Angela Perz, Nadia Fuellbrunn, Stephan Kiontke, Lars Langemeyer, Dovile Januliene, Kilian Schnelle, Daniel Kuemmel, Florian Froehlich, Arne Moeller, Christian Ungermann
Summary: Lysosomes are crucial for cell survival and function, and the HOPS complex plays a key role in lysosomal fusion. In this study, we used cryo-electron microscopy to examine the structure of HOPS and found that its flexibility is limited to the GTPase binding region. The SNARE-binding module is firmly attached to the core, positioning it ideally for membrane fusion.
Article
Biochemistry & Molecular Biology
Henning Arlt, Babu Raman, Yasmina Filali-Mouncef, Yan Hu, Alexandre Leytens, Ralph Hardenberg, Rodrigo Guimaraes, Franziska Kriegenburg, Muriel Mari, Iwona I. Smaczynska-de Rooij, Kathryn R. Ayscough, Christian Ungermann, Joern Dengjel, Fulvio Reggiori
Summary: Autophagy is a crucial cellular process that maintains homeostasis by degrading cellular components. This study reveals that Vps1 mutants affect the subcellular distribution of Atg9 and impair autophagy. The findings provide new insights into the role of dynamins in Atg9 trafficking and their potential contribution to severe human pathologies associated with autophagy defects.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Kalliopi Sofou, Kolja Meier, Leslie E. Sanderson, Debora Kaminski, Laia Montoliu-Gaya, Emma Samuelsson, Maria Blomqvist, Lotta Agholme, Jutta Gaertner, Chris Muehlhausen, Niklas Darin, Tahsin Stefan Barakat, Lars Schlotawa, Tjakko van Ham, Jorge Asin Cayuela, Fredrik H. Sterky
Summary: Patients with lysosomal storage disease-like symptoms were found to have homozygous mutations in VPS16, resulting in impaired cellular functions such as transferrin uptake and lysosomal accumulation, which were rescued by re-expression of VPS16. Disrupted vps16 expression in zebrafish led to developmental defects and similar lysosomal and autophagosomal accumulation in the brain. This expands the understanding of diseases resulting from mutations in HOPS/CORVET subunits.
EMBO MOLECULAR MEDICINE
(2021)
Article
Biology
Hongki Song, William T. Wickner, Adam Linstedt
Summary: The yeast vacuolar membrane fusion process can be achieved using a synthetic tether instead of the HOPS complex. This suggests that Sec17 and Sec18 play a crucial role in membrane fusion and may have a general role in promoting fusion across different cellular processes.
Article
Biochemistry & Molecular Biology
Emma L. Clayton, Katherine Bonnycastle, Adrian M. Isaacs, Michael A. Cousin, Stephanie Schorge
Summary: Mutations in the ESCRT-III subunit CHMP2B lead to a novel synaptopathy characterized by selective retention of presynaptic SV trafficking proteins and defective SV recycling in neurons. This unique synaptic pathology may represent a key early event in various forms of FTD, as proteins associated with genetic FTD forms localize at the presynapse.
JOURNAL OF NEUROCHEMISTRY
(2022)