{"title":"Microtubule function and dysfunction in the nervous system","authors":"Eun-Hae Jang , Harryn Choi , Eun-Mi Hur","doi":"10.1016/j.mocell.2024.100111","DOIUrl":"10.1016/j.mocell.2024.100111","url":null,"abstract":"<div><div>Microtubules are core components of the neuronal cytoskeleton, providing structural support for the complex cytoarchitecture of neurons and serving as tracks for long-distance transport. The properties and functions of neuronal microtubules are controlled by tubulin isoforms and a variety of post-translational modifications, collectively known as the “tubulin code.” The tubulin code exerts direct control over the intrinsic properties of neuronal microtubules and regulates the repertoire of proteins that read the code, which in turn, has a significant impact on microtubule stability and dynamics. Here, we review progress in the understanding of the tubulin code in the nervous system, with a particular focus on tubulin post-translational modifications that have been proposed as potential contributors to the development and maintenance of the mammalian nervous system. Furthermore, we also discuss the potential links between disruptions in the tubulin code and neurological disorders, including neurodevelopmental abnormalities and neurodegenerative diseases.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 10","pages":"Article 100111"},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291500","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":"Simple methods to determine the dissociation constant, Kd","authors":"Donghun Lee, Juwon Kim, Gwangrog Lee","doi":"10.1016/j.mocell.2024.100112","DOIUrl":"10.1016/j.mocell.2024.100112","url":null,"abstract":"<div><div>The determination of the dissociation constant (K<sub>d</sub>) is pivotal in biochemistry and pharmacology for understanding binding affinities in chemical reactions, which is crucial for drug development and comprehending biological systems. Here, we introduce a single-molecule fluorescence resonance energy transfer–based method for determining K<sub>d</sub>, alongside the conventional electrophoretic mobility shift assay method of K<sub>d</sub>, offering insights into thermodynamic interactions between proteins and substrates. The single-molecule fluorescence resonance energy transfer approach is highlighted for its ability to accurately measure binding and dissociation kinetics through fluorescence labeling and the intrinsic nature of protein-DNA interactions, representing a significant advancement in the fields of molecular biology and pharmacology.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 10","pages":"Article 100112"},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291501","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}
Jinseul Kyung , Daesong Jeong , Hyunjoo Eom , Jeesoo Kim , Jong-Seo Kim , Ilha Lee
{"title":"C-TERMINAL DOMAIN PHOSPHATASE-LIKE 1 promotes flowering with TAF15b by repressing the floral repressor gene FLOWERING LOCUS C","authors":"Jinseul Kyung , Daesong Jeong , Hyunjoo Eom , Jeesoo Kim , Jong-Seo Kim , Ilha Lee","doi":"10.1016/j.mocell.2024.100114","DOIUrl":"10.1016/j.mocell.2024.100114","url":null,"abstract":"<div><div><em>Arabidopsis</em> TATA-BINDING PROTEIN-ASSOCIATED FACTOR15b (TAF15b) is a plant-specific component of the transcription factor IID complex. TAF15b is involved in the autonomous pathway for flowering and represses the transcription of <em>FLOWERING LOCUS C</em> (<em>FLC</em>)<em>,</em> a major floral repressor in <em>Arabidopsis</em>. While components of the autonomous flowering pathway have been extensively studied, scant attention has been directed toward elucidating the direct transcriptional regulators responsible for repressing <em>FLC</em> transcription. Here, we demonstrate that C-TERMINAL DOMAIN PHOSPHATASE-LIKE 1 (CPL1) is a physical and functional partner of TAF15b, playing a role in <em>FLC</em> repression. CPL1 is a protein phosphatase that dephosphorylates the C-terminal domain of RNA polymerase II (Pol II). Through the immunoprecipitation and mass spectrometry technique, we identified CPL1 as an interacting partner of TAF15b. Similar to <em>taf15b</em>, the <em>cpl1</em> mutant showed a late-flowering phenotype caused by an increase in <em>FLC</em> levels. Additionally, the increase in <em>cpl1</em> was correlated with the enrichment of phosphorylated Pol II in the <em>FLC</em> chromatin, as expected. We also discovered that CPL1 and TAF15b share additional common target genes through transcriptome analysis. These results suggest that TAF15b and CPL1 cooperatively repress transcription through the dephosphorylation of Pol II, especially at the <em>FLC</em> locus.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 10","pages":"Article 100114"},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291498","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":"Cover and caption","authors":"","doi":"10.1016/S1016-8478(24)00157-2","DOIUrl":"10.1016/S1016-8478(24)00157-2","url":null,"abstract":"","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 10","pages":"Article 100132"},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526971","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}
Eun Jo Du , MinHyuk Lee , Seon Yeong Kim , Se Hoon Park , Hye-Jung Ohk , KyeongJin Kang
{"title":"Linkage of alternative exon assembly in Drosophila TrpA1 transcripts","authors":"Eun Jo Du , MinHyuk Lee , Seon Yeong Kim , Se Hoon Park , Hye-Jung Ohk , KyeongJin Kang","doi":"10.1016/j.mocell.2024.100110","DOIUrl":"10.1016/j.mocell.2024.100110","url":null,"abstract":"<div><div><em>Drosophila TrpA1</em> (<em>transient receptor potential ankyrin 1</em>) transcripts are alternatively spliced at 2 distinct sites each with a choice of mutually exclusive exons. The first site determines exon1 encoding the amino terminus to produce either nucleophile-, electrophile- and noxious temperature-gated TRPA1(A) or electrophile- and innocuous warmth-gated TRPA1(B). The second site selects for exon10, resulting in <em>TrpA1</em> variants with either exon10a or exon10b encoding a domain between the N-terminal ankyrin repeats and the transmembrane segments. Although unbiased assembly would generate TRPA1 with 4 different domain combinations, the functional impact of these alternative domains remains to be thoroughly examined. Here, we find that there is a relatively strong linkage in mRNA splicing between the 2 sites in the case of <em>TrpA1(B)</em>, but not <em>TrpA1(A)</em>, transcripts. Our semiquantitative assay, consisting of reverse transcription polymerase chain reaction and Sanger sequencing, revealed that exon10b is little coupled with <em>TrpA1(B)</em> transcripts, suggesting that only 3 isoforms, TRPA1(A)-exon10a [denoted as TRPA1(A)], TRPA1(A)-exon10b [TRPA1(A)10b], and TRPA1(B)-exon10a [TRPA1(B)], are present at detectable levels using our method. Interestingly, heterologously expressed TRPA1(A)10b showed elevated sensitivity to low concentrations of N-methyl maleimide, a cysteine-modifying electrophile, compared with other isoforms. Equivalent isoforms in malaria-transmitting <em>Anopheles gambiae</em> displayed a similar pattern of isoform-dependent N-methyl maleimide dose dependences, suggesting that the chemosensory regulation by selective domain assembly is conserved in insect TRPA1s. Thus, alternative RNA splicing of exon10 is coordinated in conjunction with the first exons, regulating chemical sensitivity of insect TRPA1s.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 10","pages":"Article 100110"},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291499","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":"Cover and caption","authors":"","doi":"10.1016/S1016-8478(24)00140-7","DOIUrl":"10.1016/S1016-8478(24)00140-7","url":null,"abstract":"","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 9","pages":"Article 100115"},"PeriodicalIF":3.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1016847824001407/pdfft?md5=8e4b4f1941e48689c93fa16b50e1c0ed&pid=1-s2.0-S1016847824001407-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241350","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}
Yejin Kim , Christian Danve M. Castroverde , Jong Hum Kim
{"title":"Natural allelic diversity of the calcium signaling regulators in plants","authors":"Yejin Kim , Christian Danve M. Castroverde , Jong Hum Kim","doi":"10.1016/j.mocell.2024.100104","DOIUrl":"10.1016/j.mocell.2024.100104","url":null,"abstract":"<div><p>Calcium ions act as secondary messengers in diverse signaling pathways in plants throughout their life cycle. Studies have revealed that calcium is involved in developmental events and in responses to external stimuli, such as biotic and abiotic stresses. Cellular calcium ion levels are tightly controlled by intricate molecular machinery such as calcium channels and pumps. Transient and spatial fluctuations in calcium levels are subsequently recognized by diverse calcium-decoding molecules, resulting in signal transduction. In this review, we highlight recent findings on natural variations in genes controlling calcium signaling in diverse plant biological processes. We then show how the calcium ion context is utilized by fine-tuning the natural variation in centrally important genes.</p></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 9","pages":"Article 100104"},"PeriodicalIF":3.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1016847824001298/pdfft?md5=1e7bb52a005033378364e4bb2a58aed8&pid=1-s2.0-S1016847824001298-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889703","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":"Cover and caption","authors":"","doi":"10.1016/S1016-8478(24)00130-4","DOIUrl":"10.1016/S1016-8478(24)00130-4","url":null,"abstract":"","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 8","pages":"Article 100105"},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1016847824001304/pdfft?md5=ae93a44b2d8d09d882067b3296002c00&pid=1-s2.0-S1016847824001304-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142011662","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}