{"id":2545,"date":"2015-06-17T00:00:00","date_gmt":"2015-06-17T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/protein-plays-unexpected-role-in-embryonic-stem-cells\/"},"modified":"2015-06-17T00:00:00","modified_gmt":"2015-06-17T07:00:00","slug":"protein-plays-unexpected-role-in-embryonic-stem-cells","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/protein-plays-unexpected-role-in-embryonic-stem-cells\/","title":{"rendered":"Protein plays unexpected role in embryonic stem cells"},"content":{"rendered":"

\nLA JOLLA\u2013What if you found out that pieces of your front door were occasionally flying off the door frame to carry out chores around the house? That\u2019s the kind of surprise scientists at the Salk Institute experienced with their recent discovery that nucleoporins\u2013proteins that act as cellular \u201cdoorways\u201d to help manage what goes in and out of a cell\u2019s nucleus\u2013are actually much bigger players in expressing genes than previously thought.\n<\/p>\n

\nThe finding, published June 16, 2015 in the journal Genes & Development<\/em><\/a>, shows that nucleoporins play an important role in maintaining embryonic stem cells before they begin to develop into specific tissues. This discovery gives a new understanding to genetic diseases that are caused by mutations in these proteins. One nucleoporin protein in particular has a dramatic\u2013and unanticipated\u2013function in the formation of neurons from stem cells.\n<\/p>\n

\"\"<\/p>\n

Scientists discovered that a protein called Nup153 (green) control how embryonic stem cells (blue) develop. When Salk scientists deleted Nup153 (left), the cells were free to rapidly begin to turn into the precursors of neurons (marked in red), suggesting a previously unknown role for Nup153.<\/p>\n

Click here<\/a> for a high-resolution image.<\/p>\n

\nImage: Courtesy of the Salk Institute for Biological Studies\n<\/p>\n<\/div>\n

\n\u201cWe\u2019ve shone a new light on this class of proteins,\u201d says Martin Hetzer<\/a>, a professor in Salk\u2019s \u5206\u5b50\u4e0e\u7ec6\u80de\u751f\u7269\u5b66\u5b9e\u9a8c\u5ba4<\/a> and senior author of the new paper. \u201cI hope people start to accept and realize that nucleoporins are more than just transport proteins.\u201d\n<\/p>\n

\nNucleoporins\u2013of which there are about 30 versions\u2013are typically part of nuclear pore complexes, giant structures that connect the inside of a cell\u2019s nucleus to the outer cytoplasm. In 2010, Hetzer\u2019s team first uncovered hints that nucleoporins may also have a role in regulating the timing of when genes inside the nucleus are transcribed into proteins during a cell\u2019s development. But exactly what that role might be was unclear.\n<\/p>\n

\nIn the new work, Hetzer and his colleagues focused on one particular nucleoporin called Nup153, which is known to rapidly move on and off of the nuclear pore complex, suggesting it might be doing something other than providing structural support to the pore.\n<\/p>\n

\nThe researchers turned to mouse embryonic stem cells\u2013cells that have the potential to differentiate into any cell type in the body\u2013and deleted Nup153. They expected that if Nup153 played a key role in cell differentiation, then removing it from stem cells would stop them from differentiating. Instead, the opposite happened.\n<\/p>\n

\n\u201cThe big surprise was that when we took out this gene, the stem cells started to differentiate,\u201d said Hetzer. \u201cAnd not only did they start to differentiate, but they started to differentiate into neurons.\u201d\n<\/p>\n

\"\"<\/p>\n

\nMartin Hetzer and Filipe Jacinto of the Molecular and Cell Biology Laboratory <\/p>\n

Click here<\/a> for a high-resolution image.<\/p>\n

\nImage: Courtesy of the Salk Institute for Biological Studies\n<\/p>\n<\/div>\n

\nNup153, researchers discovered, put the brakes on certain genes that need to be turned on for stem cells to turn into brain cells. When the brakes are lifted, the stem cells start differentiating.\n<\/p>\n

\n\u201cThis study not only revealed a critical function for nucleoporins in mediating the undifferentiated state of embryonic stem cells by silencing neural genes, but also introduced new mechanistic directions for elucidating the role of these proteins during mammalian development,\u201d says Filipe Jacinto, a postdoctoral researcher in Hetzer\u2019s lab and first author of the paper.\n<\/p>\n

\nHetzer suspects that other nucleoporins also have roles in gene expression control, but cautions that the roles could be very different\u2013each nucleoporin, he says, likely targets a different set of genes, and some might activate the genes rather than repress them.\n<\/p>\n

\nMutations in many nucleoporin genes has been linked to human diseases and developmental disorders, including some forms of leukemia and inherited heart problems. Until now, Hetzer says, researchers have assumed the mutations led to disease by altering the transport of proteins in and out of a cell\u2019s nucleus. \u201cNow, we\u2019re realizing this is probably not the only explanation,\u201d he says. \u201cMany of those diseases and developmental disorders might actually be caused by the ability of these genes to regulate gene expression programs.\u201d\n<\/p>\n

\nHis lab is planning to follow up with studies on Nup153, and exactly how it\u2019s recruited to genes, as well as investigating the developmental roles of other nucleoporins.\n<\/p>\n

\nChris Benner, director of the Integrative Genomics and Bioinformatics Core<\/a> at the Salk Institute, also contributed to the work.\n<\/p>\n

\nThe work and the researchers involved were supported by grants from the National Institutes of Health<\/a> and the National Cancer Institute<\/a>.\n<\/p>\n

\nAbout the Salk Institute for Biological Studies:<\/strong>
\nThe Salk Institute for Biological Studies is one of the world’s preeminent basic research institutions, where internationally renowned faculty probes fundamental life science questions in a unique, collaborative and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer’s, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.<\/p>\n

Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, MD, the Institute is an independent nonprofit organization and architectural landmark.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[86],"disease-research":[],"class_list":["post-2545","disclosure","type-disclosure","status-publish","hentry","faculty-martin-hetzer"],"acf":[],"yoast_head":"\nProtein plays unexpected role in embryonic stem cells - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/protein-plays-unexpected-role-in-embryonic-stem-cells\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Protein plays unexpected role in embryonic stem cells - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2013What if you found out that pieces of your front door were occasionally flying off the door frame to carry out chores around the house? 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