01992nas a2200205   4500008004100000022001400041245010600055210006900161260007900230300001400309490000800323520120900331100001801540700002001558700002101578700001801599700002001617700002401637856012501661       2015                        eng d  a0006-349500aMolecular mechanism underlying recruitment and insertion of lipid-anchored LC3 protein into membranes0 aMolecular mechanism underlying recruitment and insertion of lipi  a600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USAbCELL PRESScNOV  a2067-20780 v1093 a<p>Lipid modification of cytoplasmic proteins initiates membrane engagement that triggers diverse cellular processes. Despite the abundance of lipidated proteins in the human proteome, the key determinants underlying membrane recognition and insertion are poorly understood. Here, we define the course of spontaneous membrane insertion of LC3 protein modified with phosphatidylethanolamine using multiple coarse-grain simulations. The partitioning of the lipid anchor chains proceeds through a concerted process, with its two acyl chains inserting one after the other. Concurrently, a conformational rearrangement involving the alpha-helix III of LC3, especially in the three basic residues Lys(65), Arg(68), and Arg(69), ensures stable insertion of the phosphatidylethanolamine anchor into membranes. Mutational studies validate the crucial role of these residues, and further live-cell imaging analysis shows a substantial reduction in the formation of autophagic vesicles for the mutant proteins. Our study captures the process of water-favored LC3 protein recruitment to the membrane and thus opens, to our knowledge, new avenues to explore the cellular dynamics underlying vesicular trafficking.</p>1 aThukral, Lipi1 aSengupta, Durba1 aRamkumar, Amrita1 aMurthy, Divya1 aAgrawal, Nikhil1 aGokhale, Rajesh, S.  uhttps://library.ncl.res.in/content/molecular-mechanism-underlying-recruitment-and-insertion-lipid-anchored-lc3-protein-002613nas a2200361   4500008004100000245010900041210006900150260000800219490000600227520145100233100001901684700002801703700001701731700002001748700002001768700001701788700001901805700001901824700002001843700001801863700002501881700002101906700002101927700001801948700001801966700002901984700002302013700002102036700002502057700001602082700002402098856012902122       2017                        eng d00aMapping architectural and transcriptional alterations in non-lesional and lesional epidermis in vitiligo0 aMapping architectural and transcriptional alterations in nonlesi  cAUG0 v73 aIn vitiligo, chronic loss of melanocytes and consequent absence of melanin from the epidermis presents a challenge for long-term tissue maintenance. The stable vitiligo patches are known to attain an irreversible depigmented state. However, the molecular and cellular processes resulting in this remodeled tissue homeostasis is unclear. To investigate the complex interplay of inductive signals and cell intrinsic factors that support the new acquired state, we compared the matched lesional and non-lesional epidermis obtained from stable non-segmental vitiligo subjects. Hierarchical clustering of genome-wide expression of transcripts surprisingly segregated lesional and non-lesional samples in two distinct clades, despite the apparent heterogeneity in the lesions of different vitiligo subjects. Pathway enrichment showed the expected downregulation of melanogenic pathway and a significant downregulation of cornification and keratinocyte differentiation processes. These perturbations could indeed be recapitulated in the lesional epidermal tissue, including blunting of rete-ridges, thickening of stratum corneum and increase in the size of corneocytes. In addition, we identify marked increase in the putrescine levels due to the elevated expression of spermine/spermidine acetyl transferase. Our study provides insights into the intrinsic self-renewing ability of damaged lesional tissue to restore epidermal functionality in vitiligo.1 aSingh, Archana1 aGotherwal, Vishvabandhu1 aJunni, Paivi1 aVijayan, Vinaya1 aTiwari, Manisha1 aGanju, Parul1 aKumar, Avinash1 aSharma, Pankaj1 aFatima, Tanveer1 aGupta, Aayush1 aHolla, Ananthaprasad1 aKar, Hemanta, K.1 aKhanna, Sangeeta1 aThukral, Lipi1 aMalik, Garima1 aNatarajan, Krishnamurthy1 aGadgil, Chetan, J.1 aLahesmaa, Riitta1 aNatarajan, Vivek, T.1 aRani, Rajni1 aGokhale, Rajesh, S.  uhttps://library.ncl.res.in/content/mapping-architectural-and-transcriptional-alterations-non-lesional-and-lesional-epidermis