Luca Masin, Steven Bergmans, Annelies Van Dyck, Karl Farrow, Lies De Groef, Lieve Moons
{"title":"Local glycolysis supports injury-induced axonal regeneration.","authors":"Luca Masin, Steven Bergmans, Annelies Van Dyck, Karl Farrow, Lies De Groef, Lieve Moons","doi":"10.1083/jcb.202402133","DOIUrl":"10.1083/jcb.202402133","url":null,"abstract":"<p><p>Successful axonal regeneration following injury requires the effective allocation of energy. How axons withstand the initial disruption in mitochondrial energy production caused by the injury and subsequently initiate regrowth is poorly understood. Transcriptomic data showed increased expression of glycolytic genes after optic nerve crush in retinal ganglion cells with the co-deletion of Pten and Socs3. Using retinal cultures in a multicompartment microfluidic device, we observed increased regrowth and enhanced mitochondrial trafficking in the axons of Pten and Socs3 co-deleted neurons. While wild-type axons relied on mitochondrial metabolism, after injury, in the absence of Pten and Socs3, energy production was supported by local glycolysis. Specific inhibition of lactate production hindered injury survival and the initiation of regrowth while slowing down glycolysis upstream impaired regrowth initiation, axonal elongation, and energy production. Together, these observations reveal that glycolytic ATP, combined with sustained mitochondrial transport, is essential for injury-induced axonal regrowth, providing new insights into the metabolic underpinnings of axonal regeneration.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dachsous and Fat coordinately repress the Dachs-Dlish-Approximated complex to control growth.","authors":"Hitoshi Matakatsu, Richard G Fehon","doi":"10.1083/jcb.202406119","DOIUrl":"10.1083/jcb.202406119","url":null,"abstract":"<p><p>Two protocadherins, Dachsous and Fat, regulate organ growth in Drosophila via the Hippo pathway. Dachsous and Fat bind heterotypically to regulate the abundance and subcellular localization of a \"core complex\" consisting of Dachs, Dlish, and Approximated. This complex localizes to the junctional cortex where it represses Warts. Dachsous is believed to promote growth by recruiting and stabilizing this complex, while Fat represses growth by promoting its degradation. Here, we examine the functional relationships between the intracellular domains of Dachsous and Fat and the core complex. While Dachsous promotes the accumulation of core complex proteins in puncta, it is not required for their assembly. Indeed, the core complex accumulates maximally in the absence of both Dachsous and Fat. Furthermore, Dachsous represses growth in the absence of Fat by removing the core complex from the junctional cortex. Fat similarly recruits core complex components but promotes their degradation. Our findings reveal that Dachsous and Fat coordinately constrain tissue growth by repressing the core complex.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"BEACH domain proteins in membrane trafficking and disease.","authors":"Conceição Pereira, David C Gershlick","doi":"10.1083/jcb.202410147","DOIUrl":"10.1083/jcb.202410147","url":null,"abstract":"<p><p>Two recent papers by Szentgyörgyi et al. (http://doi.org/10.1083/jcb.202401167) and Pankiv et al. (http://doi.org/10.1083/jcb.202408173) provide new insights into the roles of BEACH domain proteins in membrane trafficking and cellular homeostasis. They explore which membranes they are recruited to, how they are recruited, and the potential coat-like functions of these proteins.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rania Garde, Annisa Dea, Madeline F Herwig, Asif Ali, David Pincus
{"title":"Feedback control of the heat shock response by spatiotemporal regulation of Hsp70.","authors":"Rania Garde, Annisa Dea, Madeline F Herwig, Asif Ali, David Pincus","doi":"10.1083/jcb.202401082","DOIUrl":"10.1083/jcb.202401082","url":null,"abstract":"<p><p>Cells maintain homeostasis via dynamic regulation of stress response pathways. Stress pathways transiently induce response regulons via negative feedback loops, but the extent to which individual genes provide feedback has not been comprehensively measured for any pathway. Here, we disrupted the induction of each gene in the Saccharomyces cerevisiae heat shock response (HSR) and quantified cell growth and HSR dynamics following heat shock. The screen revealed a core feedback loop governing the expression of the chaperone Hsp70 reinforced by an auxiliary feedback loop controlling Hsp70 subcellular localization. Mathematical modeling and live imaging demonstrated that multiple HSR targets converge to promote Hsp70 nuclear localization via its release from cytosolic condensates. Following ethanol stress, a distinct set of factors similarly converged on Hsp70, suggesting that nonredundant subsets of the HSR regulon confer feedback under different conditions. Flexible spatiotemporal feedback loops may broadly organize stress response regulons and expand their adaptive capacity.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuanjiao Du, Xinyu Fan, Chunyu Song, Weiping Chang, Juan Xiong, Lin Deng, Wei-Ke Ji
{"title":"Sec23IP recruits VPS13B/COH1 to ER exit site-Golgi interface for tubular ERGIC formation.","authors":"Yuanjiao Du, Xinyu Fan, Chunyu Song, Weiping Chang, Juan Xiong, Lin Deng, Wei-Ke Ji","doi":"10.1083/jcb.202402083","DOIUrl":"10.1083/jcb.202402083","url":null,"abstract":"<p><p>VPS13B/COH1 is the only known causative factor for Cohen syndrome, an early-onset autosomal recessive developmental disorder with intellectual inability, developmental delay, joint hypermobility, myopia, and facial dysmorphism as common features, but the molecular basis of VPS13B/COH1 in pathogenesis remains largely unclear. Here, we identify Sec23 interacting protein (Sec23IP) at the ER exit site (ERES) as a VPS13B adaptor that recruits VPS13B to ERES-Golgi interfaces. VPS13B interacts directly with Sec23IP via the VPS13 adaptor binding domain (VAB), and the interaction promotes the association between ERES and the Golgi. Disease-associated missense mutations of VPS13B-VAB impair the interaction with Sec23IP. Knockout of VPS13B or Sec23IP blocks the formation of tubular ERGIC, an unconventional cargo carrier that expedites ER-to-Golgi transport. In addition, depletion of VPS13B or Sec23IP delays ER export of procollagen, suggesting a link between procollagen secretion and joint laxity in patients with Cohen disease. Together, our study reveals a crucial role of VPS13B-Sec23IP interaction at the ERES-Golgi interface in the pathogenesis of Cohen syndrome.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Serhiy Pankiv, Anette Kathinka Dahl, Aleksander Aas, Rosa Linn Andersen, Andreas Brech, Petter Holland, Sakshi Singh, Christian Bindesbøll, Anne Simonsen
{"title":"BEACH domain proteins function as cargo-sorting adaptors in secretory and endocytic pathways.","authors":"Serhiy Pankiv, Anette Kathinka Dahl, Aleksander Aas, Rosa Linn Andersen, Andreas Brech, Petter Holland, Sakshi Singh, Christian Bindesbøll, Anne Simonsen","doi":"10.1083/jcb.202408173","DOIUrl":"10.1083/jcb.202408173","url":null,"abstract":"<p><p>We identify BEACH domain-containing proteins (BDCPs) as novel membrane coat proteins involved in the sorting of transmembrane proteins (TMPs) on the trans-Golgi network and tubular sorting endosomes. The seven typical mammalian BDCPs share a predicted alpha-solenoid-beta propeller structure, suggesting they have a protocoatomer origin and function. We map the subcellular localization of seven BDCPs based on their dynamic colocalization with RAB and ARF small GTPases and identify five typical BDCPs on subdomains of dynamic tubular-vesicular compartments on the intersection of endocytic recycling and post-Golgi secretory pathways. We demonstrate that BDCPs interact directly with the cytosolic tails of selected TMPs and identify a subset of TMPs, whose trafficking to the plasma membrane is affected in cells lacking BDCP. We propose that the competitive binding of BDCPs and clathrin coat adaptors to the cytosolic tails of TMPs, followed by their clustering to distinct subdomains of secretory/recycling tubules function as a mechanism for sorting of TMPs in pleomorphic tubular-vesicular compartments that lack a clathrin coat.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yeonji Chung, Chewon Yim, Gilberto P Pereira, Sungjoon Son, Lisbeth R Kjølbye, Lauren E Mazurkiewicz, Amy M Weeks, Friedrich Förster, Gunnar von Heijne, Paulo C T Souza, Hyun Kim
{"title":"Spc2 modulates substrate- and cleavage site-selection in the yeast signal peptidase complex.","authors":"Yeonji Chung, Chewon Yim, Gilberto P Pereira, Sungjoon Son, Lisbeth R Kjølbye, Lauren E Mazurkiewicz, Amy M Weeks, Friedrich Förster, Gunnar von Heijne, Paulo C T Souza, Hyun Kim","doi":"10.1083/jcb.202211035","DOIUrl":"10.1083/jcb.202211035","url":null,"abstract":"<p><p>Secretory proteins are critically dependent on the correct processing of their signal sequence by the signal peptidase complex (SPC). This step, which is essential for the proper folding and localization of proteins in eukaryotic cells, is still not fully understood. In eukaryotes, the SPC comprises four evolutionarily conserved membrane subunits (Spc1-3 and Sec11). Here, we investigated the role of Spc2, examining SPC cleavage efficiency on various models and natural signal sequences in yeast cells depleted of or with mutations in Spc2. Our data show that discrimination between substrates and identification of the cleavage site by SPC is compromised when Spc2 is absent or mutated. Molecular dynamics simulation of the yeast SPC AlphaFold2-Multimer model indicates that membrane thinning at the center of SPC is reduced without Spc2, suggesting a molecular explanation for the altered substrate recognition properties of SPC lacking Spc2. These results provide new insights into the molecular mechanisms by which SPC governs protein biogenesis.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Susan A Gerbi, Virginia A Zakian, Elizabeth H Blackburn
{"title":"Joseph G. Gall (1928-2024): Cell biologist, naturalist, and mentor extraordinaire.","authors":"Susan A Gerbi, Virginia A Zakian, Elizabeth H Blackburn","doi":"10.1083/jcb.202410071","DOIUrl":"10.1083/jcb.202410071","url":null,"abstract":"<p><p>Joseph Grafton Gall (1928-2024), a founder of modern cell biology, made foundational discoveries on eukaryotic chromosomes and RNA biogenesis. His major contributions include the development of in situ hybridization (later called FISH), demonstration of one DNA double helix/chromosome, isolation of the first eukaryote gene, localization of satellite DNA to centromeric heterochromatin, determination of the first telomeric DNA sequence, and elucidating the structure and functions of Cajal bodies. He was an expert microscopist, a scholar of science history, and an avid naturalist. These attributes, together with his ready embrace of new technologies, contributed to his remarkable success. He was also an early and strong supporter of women in science. His contributions to science and mentoring were recognized by numerous awards including the American Society for Cell Biology's E.B. Wilson Medal, the Society for Developmental Biology's Lifetime Achievement Award, the Albert Lasker Special Achievement Award in Medical Research, and the AAAS Mentor Award for Lifetime Achievement.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Rita Dias Araújo, Abdoul Akim Bello, Joëlle Bigay, Céline Franckhauser, Romain Gautier, Julie Cazareth, Dávid Kovács, Frédéric Brau, Nicolas Fuggetta, Alenka Čopič, Bruno Antonny
{"title":"Surface tension-driven sorting of human perilipins on lipid droplets.","authors":"Ana Rita Dias Araújo, Abdoul Akim Bello, Joëlle Bigay, Céline Franckhauser, Romain Gautier, Julie Cazareth, Dávid Kovács, Frédéric Brau, Nicolas Fuggetta, Alenka Čopič, Bruno Antonny","doi":"10.1083/jcb.202403064","DOIUrl":"10.1083/jcb.202403064","url":null,"abstract":"<p><p>Perilipins (PLINs), the most abundant proteins on lipid droplets (LDs), display similar domain organization including amphipathic helices (AH). However, the five human PLINs bind different LDs, suggesting different modes of interaction. We established a minimal system whereby artificial LDs covered with defined polar lipids were transiently deformed to promote surface tension. Binding of purified PLIN3 and PLIN4 AH was strongly facilitated by tension but was poorly sensitive to phospholipid composition and to the presence of diacylglycerol. Accordingly, LD coverage by PLIN3 increased as phospholipid coverage decreased. In contrast, PLIN1 bound readily to LDs fully covered by phospholipids; PLIN2 showed an intermediate behavior between PLIN1 and PLIN3. In human adipocytes, PLIN3/4 were found in a soluble pool and relocated to LDs upon stimulation of fast triglyceride synthesis, whereas PLIN1 and PLIN2 localized to pre-existing LDs, consistent with the large difference in LD avidity observed in vitro. We conclude that the PLIN repertoire is adapted to handling LDs with different surface properties.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julie M J Verhoef, Cas Boshoven, Felix Evers, Laura J Akkerman, Barend C A Gijsbrechts, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Akhil B Vaidya, Taco W A Kooij
{"title":"Detailing organelle division and segregation in Plasmodium falciparum.","authors":"Julie M J Verhoef, Cas Boshoven, Felix Evers, Laura J Akkerman, Barend C A Gijsbrechts, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Akhil B Vaidya, Taco W A Kooij","doi":"10.1083/jcb.202406064","DOIUrl":"10.1083/jcb.202406064","url":null,"abstract":"<p><p>The malaria-causing parasite, P. falciparum, replicates through schizogony, a tightly orchestrated process where numerous daughter parasites are formed simultaneously. Proper division and segregation of one-per-cell organelles, like the mitochondrion and apicoplast, are essential, yet remain poorly understood. We developed a new reporter parasite line that allows visualization of the mitochondrion in blood and mosquito stages. Using high-resolution 3D imaging, we found that the mitochondrion orients in a cartwheel structure, prior to stepwise, non-geometric division during last-stage schizogony. Analysis of focused ion beam scanning electron microscopy data confirmed these mitochondrial division stages. Furthermore, these data allowed us to elucidate apicoplast division steps, highlighted its close association with the mitochondrion, and showed putative roles of the centriolar plaques in apicoplast segregation. These observations form the foundation for a new detailed mechanistic model of mitochondrial and apicoplast division and segregation during P. falciparum schizogony and pave the way for future studies into the proteins and protein complexes involved in organelle division and segregation.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}