{"title":"Ehg1/May24 stabilizes yeast amino acid permease by facilitating its localization to lipid rafts under high hydrostatic pressure.","authors":"Yusuke Kato, Takahiro Mochizuki, Tetsuo Mioka, Takuma Kishimoto, Fumiyoshi Abe","doi":"10.1091/mbc.E25-02-0067","DOIUrl":"10.1091/mbc.E25-02-0067","url":null,"abstract":"<p><p>Pressure is a thermodynamic parameter that influences chemical equilibrium and reaction kinetics; however, its effects on complex cellular mechanisms remain largely unexplored. In this study, we investigated the role of Ehg1 (also known as May24), a novel endoplasmic reticulum (ER) membrane protein in <i>Saccharomyces cerevisiae</i>, in the stabilization of tryptophan permease Tat2, which ensures cell growth under high hydrostatic pressure (∼25 MPa, megapascals). We show that Ehg1 in the cortical ER (cER) physically interacts with the plasma membrane Tat2 <i>in trans</i> and plays a vital role in preserving its localization in the plasma membrane by facilitating its partitioning into the plasma membrane microdomains, lipid rafts. This stabilization depends on the contact between the cER and plasma membrane, which is critical for effective nutrient transport under pressure, as evidenced from the fact that Tat2 was destabilized in Δtether and Δ-super-tether strains lacking such contact. These insights into the regulation of nutrient permease under high pressure contribute to our understanding of microbial adaptation to extreme environments.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar100"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dynamic phosphorylation of MIS12 ensures accurate kinetochore-microtubule attachment by expanding the fibrous corona.","authors":"Qi Li, Qingzhou Chen, Tao Zheng, Junlin Teng, Haining Zhou, Jianguo Chen","doi":"10.1091/mbc.E25-02-0087","DOIUrl":"10.1091/mbc.E25-02-0087","url":null,"abstract":"<p><p>Genomic integrity in mammalian cells relies on faithful chromosome segregation. Kinetochores capture microtubules and establish robust kinetochore-microtubule attachment to achieve accurate segregation. The MIS12 complex, a tetramer comprising MIS12, DSN1, NSL1, and PMF1, plays a critical role in kinetochore-microtubule attachment. However, how the MIS12 complex functions at the kinetochore-microtubule interface is not fully understood. Here, we found that MIS12 is phosphorylated at Ser177 by NEK2A from prophase to prometaphase. Phosphorylation of MIS12 expands the projection of the outer kinetochore, known as the fibrous corona, thus facilitating the attachment of kinetochores to microtubules. When chromosomes align at the equatorial plate, Ser177 on MIS12 is dephosphorylated by PP1, which is required for kinetochore compaction and end-on attachment conversion. We uncovered that the dynamic phosphorylation of MIS12 regulates the expansion-compaction transition of the outermost layer of kinetochores, ensuring accurate kinetochore-microtubule attachment and faithful chromosome segregation.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br21"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Michael Patrick Sheetz, 1946-2025, a devotee of and major contributor to membrane and cytoskeletal biology.","authors":"Linda J Kenney, Ronald D Vale, James A Spudich","doi":"10.1091/mbc.E25-05-0208","DOIUrl":"https://doi.org/10.1091/mbc.E25-05-0208","url":null,"abstract":"<p><p>Michael P. Sheetz (1946-2025) advanced the field of mechanobiology through his creative experiments, new methodologies, and keen insights. His research touched many fields of cell biology, including membrane biophysics, motor proteins, the cytoskeleton, cell migration, and cellular senescence. In addition to his research, Sheetz was a leader who built vibrant academic departments and institutes and advanced the careers of many trainees.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":"36 8","pages":"fe1"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nusrat Jahan Tushi, You Lu, Zhibing Zhang, Shengyi Sun
{"title":"SEL1L regulates ER homeostasis in Sertoli cells but is dispensable for their function.","authors":"Nusrat Jahan Tushi, You Lu, Zhibing Zhang, Shengyi Sun","doi":"10.1091/mbc.E25-03-0101","DOIUrl":"10.1091/mbc.E25-03-0101","url":null,"abstract":"<p><p>Endoplasmic reticulum (ER)-associated protein degradation (ERAD) plays a vital role in maintaining ER homeostasis by degrading misfolded ER proteins. The SEL1L-HRD1 complex, the most evolutionarily conserved branch of ERAD, has been implicated in various physiological processes in both mice and humans, including cellular stress responses, immune function, and development. However, its role in Sertoli cells, which are critical for supporting spermatogenesis, remains unexplored. Here, we show that Sertoli cell SEL1L is not essential for their function or spermatogenesis. SEL1L and HRD1 proteins are expressed in Sertoli cells, and the deletion of SEL1L in Sertoli cells reduces HRD1 protein levels and impairs ERAD function. This leads to elevated ER stress responses and increased expression of ER chaperones, suggesting a potential compensatory adaptation to maintain ER homeostasis. Despite these changes, Sertoli cell-specific <i>Sel1L</i> deletion does not disrupt testicular histology, sperm count, or male fertility. These findings reveal the adaptation of Sertoli cells to SEL1L and ERAD dysfunction and highlight their ability to sustain spermatogenesis under ER stress.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar92"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Erv41-Erv46 complex serves as a retrograde receptor to retrieve misfolded secretory proteins that have escaped from the ER.","authors":"John A Fuesler, Jaime R Blais, Charles Barlowe","doi":"10.1091/mbc.E25-02-0090","DOIUrl":"10.1091/mbc.E25-02-0090","url":null,"abstract":"<p><p>The Erv41-Erv46 complex is a conserved transmembrane cargo receptor that returns endoplasmic reticulum (ER)-resident proteins that have reached the Golgi complex back to the ER. Here, we report that this retrograde receptor also retrieves misfolded secretory cargo that contain luminal domain lesions, such as CPY*. Cells lacking Erv41-Erv46, increase the cellular clearance of misfolded cargo proteins due to increased ER escape and transport to the cell surface or to the vacuole for degradation. Erv41-Erv46 displays selectivity in binding misfolded substrates compared with their folded counterparts. Binding experiments reconstituted with purified proteins demonstrate that Erv41-Erv46 complex binds directly to misfolded CPY* through a shared cargo-binding site. These findings indicate that Erv41-Erv46 acts as a post-ER protein quality control checkpoint and expand the client range by which retrograde receptors ensure delivery of correctly folded secretory proteins.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar80"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mar Martinez Pastor, Cynthia L Darnell, Angie Vreugdenhil, Amy K Schmid
{"title":"Rapid rewiring of an archaeal transcription factor function via flexible cis-trans interactions.","authors":"Mar Martinez Pastor, Cynthia L Darnell, Angie Vreugdenhil, Amy K Schmid","doi":"10.1091/mbc.E24-11-0505","DOIUrl":"10.1091/mbc.E24-11-0505","url":null,"abstract":"<p><p>For microbial cells, an appropriate response to changing environmental conditions is critical for viability. Transcription regulatory proteins, or transcription factors (TF) sense environmental signals to change gene expression. However, it remains unclear how TFs and their corresponding gene regulatory networks are selected over evolutionary time scales. The function of TFs and how they evolve are particularly understudied in archaeal organisms. Here, we identified, characterized, and compared the function of the RosR TF across three related hypersaline-adapted archaeal model species. RosR was previously characterized as a global regulator of gene expression during oxidative stress in the species <i>Halobacterium salinarum</i> (<i>hs</i>RosR). Here, we use functional genomics and quantitative phenotyping to demonstrate that, despite strong sequence conservation of RosR across species, its function diverges substantially. Surprisingly, RosR in <i>Haloferax volcanii</i> (<i>hv</i>RosR) and <i>Haloferax mediterranei</i> (<i>hm</i>RosR) regulates genes whose products function in motility and the membrane, leading to significant defects in motility when <i>RosR</i> is deleted. Given weak conservation and degeneration in cis-regulatory sequences recognized by the RosR TF across species, we hypothesize that the RosR regulatory network is readily rewired during evolution across related species of archaea.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar86"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jacob M Bouchier, Emily Knebel, Jennifer Amstutz, Gabriel Torrens, Gustavo Santiago-Collazo, Carli McCurry, Alexandra J Weisberg, Felipe Cava, Pamela J B Brown
{"title":"Activation of the ChvG-ChvI pathway promotes survival during cell wall stress in <i>Agrobacterium tumefaciens</i>.","authors":"Jacob M Bouchier, Emily Knebel, Jennifer Amstutz, Gabriel Torrens, Gustavo Santiago-Collazo, Carli McCurry, Alexandra J Weisberg, Felipe Cava, Pamela J B Brown","doi":"10.1091/mbc.E24-12-0546","DOIUrl":"10.1091/mbc.E24-12-0546","url":null,"abstract":"<p><p><i>Agrobacterium tumefaciens</i> shifts from a free-living soil bacterium to a plant-invading state upon encountering the plant root microenvironment. The acid-induced two-component sensor system ChvG-ChvI drives this shift and triggers a complex transcriptional program that promotes host invasion and survival against host immune defenses. Remarkably, ChvG-ChvI is also activated under cell wall stress conditions, suggesting that the transcriptional response may have a broader function. Here, we find that blocking cell wall synthesis either genetically or chemically leads to ChvG-ChvI activation. Mutations in key cell wall synthesis enzymes, such as penicillin-binding protein 1a and FtsW, suppress ChvG-ChvI activation in cell wall stress inducing conditions, suggesting that providing structural integrity is a primary function of the ChvG-ChvI regulon. Here, we investigated regulon components for this function. First, deletion of <i>exoA</i>, a gene required for production of the exopolysaccharide succinoglycan, confers resistance to multiple β-lactam antibiotics targeting different enzymes. Next, a class D β-lactamase is expressed that may contribute to the high level of β-lactam resistance in <i>A. tumefaciens</i>. Finally, outer membrane proteins are upregulated, suggesting that outer membrane remodeling may compensate for the accumulation of cell wall damage by providing structural integrity. Overall, we expand our understanding of mechanisms driving ChvG-ChvI activation and β-lactam resistance in a bacterial plant pathogen.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar84"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Binding of CEP152 to PLK4 stimulates kinase activity to promote centriole assembly.","authors":"Hazal Kübra Gürkaşlar, Ingrid Hoffmann","doi":"10.1091/mbc.E24-12-0581","DOIUrl":"10.1091/mbc.E24-12-0581","url":null,"abstract":"<p><p>Centriole duplication is regulated by polo-like kinase 4 (PLK4) and several conserved initiator proteins. The precise timing and regulation of PLK4 activation are critical for ensuring that centriole duplication occurs only once per cell cycle. Although significant progress has been made in understanding how PLK4 is activated, many aspects remain unclear. Here, we show how CEP152 contributes to the activation of PLK4. We utilize human cell lines that have been genetically engineered to rapidly degrade CEP152. Upon degradation of CEP152, localization of PLK4 at the proximal end of the centriole is disrupted. We show that binding of CEP152 N-terminal part to PLK4 increases phosphorylation and kinase activation. CEP152 controls the localization and levels of phosphorylated PLK4 at the proximal end of the centriole. CEP152 binding to PLK4 leads to phosphorylation and activation of PLK4 that might stabilize PLK4 dimer formation, thus allowing autophosphorylation. We propose that CEP152 activates PLK4 to ensure proper centriole duplication at the onset of S-phase.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"br17"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12327949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The midbody and midbody remnant: from cellular debris to signaling organelle with diagnostic and therapeutic potential.","authors":"Ryoko Kuriyama, J Michael Mullins, Ahna R Skop","doi":"10.1091/mbc.E25-03-0120","DOIUrl":"10.1091/mbc.E25-03-0120","url":null,"abstract":"<p><p>The midbody (MB), a transient structure formed during cytokinesis, has evolved from a mere structural component to a complex signaling organelle with diverse functions beyond cell division. Recent studies have revealed that jettisoned MB remnants (MBR) play crucial roles in intercellular communication, influencing cell fate decisions, particularly in stem cells and cancer. MBRs act as large extracellular vesicles, transferring functional RNA and proteins that modulate cell behavior, including proliferation and cancer progression. The protein KIF23, associated with MBs, is a pan-cancer marker, underscoring the clinical relevance of MB research. This review highlights the emerging significance of MBs and MBRs in cancer biology, neurobiology, and regenerative medicine, offering new avenues for diagnostic and therapeutic strategies. By reshaping our understanding of cell division and intercellular communication, these findings open exciting frontiers in cell biology with huge potential for diagnostic and therapeutic applications.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"re4"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Garret M Morton, Maria Pilar Toledo, Chunfeng Zheng, Tania Sultana, Yue J Wang, Yiming Zheng, Timothy L Megraw
{"title":"A distinct isoform of Msp300 (nesprin) organizes the perinuclear microtubule-organizing center in adipocytes.","authors":"Garret M Morton, Maria Pilar Toledo, Chunfeng Zheng, Tania Sultana, Yue J Wang, Yiming Zheng, Timothy L Megraw","doi":"10.1091/mbc.E25-01-0003","DOIUrl":"10.1091/mbc.E25-01-0003","url":null,"abstract":"<p><p>In many cell types, disparate noncentrosomal microtubule-organizing centers (ncMTOC) replace functional centrosomes and serve the unique needs of the cell types in which they form. In <i>Drosophila</i> fat body cells, an ncMTOC is organized on the nuclear surface. This perinuclear ncMTOC is anchored by the nesprin Msp300. Msp300 and the spectraplakin short stop (shot) are codependent for localization to the nuclear envelope to generate the ncMTOC, where they recruit the microtubule (MT) minus-end stabilizer Patronin (CAMSAP). The <i>Msp300</i> gene is complex, encoding at least 11 isoforms. Here, we show that two Msp300 isoforms, Msp300-PE and -PG, are required and one, Msp300-PE, appears sufficient to generate the ncMTOC. Loss of Msp300-PE/-PG impedes shot and Patronin localization to the nuclear surface and disrupts the MT array, endosomal trafficking, and nuclear positioning. Furthermore, upon loss of Msp300-PE and -PG, other Msp300 isoforms are retained at the nuclear surface despite the loss of nuclear positioning and MT organization, indicating that non-Msp300-PE/-PG isoforms are not sufficient to generate the ncMTOC. Msp300-PE has an unusual domain structure, including a lack of a KASH domain and very few spectrin repeats and appears, therefore, to have derived the function to generate an ncMTOC on the nuclear surface.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar92"},"PeriodicalIF":3.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}