Citations 3
Germline mutations in a G protein identify signaling cross-talk in T cells
Ham, Hyoungjun , Jing, Huie , Lamborn, Ian T. , Kober, M. , Anderson, David E. , Druey, Kirk M. , Mandl, Judith N. , Isidor, Bertrand , Freeman, Alexandra F. , Ganesan, Sundar , Karsak, Meliha , Mustillo, Peter , Teo, Juliana , Zolkipli‐Cunningham, Zarazuela , Lecoquierre, François , Schmid, Jana Pachlopnik , Kuhns, Douglas B. , Xu, Xuehua , Al–Herz, Waleed , Terhal, Paulien A., Muurinen, Mari , Barlogis, Vincent , Danielson, Jeffrey J. , Stewart, Helen , Rading, Sebastian, Keren, Boris , Pfundt, Rolph , Potocki, Lorraine , Olivier, Kenneth N., Faivre, Laurence , Wong, Melanie , Puel, Anne , Chou, Janet , Tusseau, Maud, Moutsopoulos, Niki M. , Matthews, Helen, Simons, Cas , Fink, Danielle , Kong, Heidi H. , Kabát, Juraj , Kim, Woo Sung , Bierhals, Tatjana , Meguro, Kazuyuki , Gu, Jingwen , Stoddard, Jennifer , Banos-Pinero, Benito, Slack, Maria A., Trivellin, Giampaolo , Mazel, Benoît , Li, Samuel T. , Watts, Val J. , Rodriguez-Quevedo, Maria F. , Bruel, Ange‐Line , Lehalle, Daphné , Torres, Daniel , Sullivan, Kathleen E. , Duffourd, Yannis, Similuk, Morgan , Blanc, Pierre , Jin, Tian, Geha, Raif S., Casanova, Jean‐Laurent , Mäkitie, Outi , Edery, Patrick , Germain, Ronald N. , Billadeau, Daniel D. , Zhang, Yu , Lenardo, Michael J. , Kober, Megan M , Koval, Alexey , Anderson, D Eric , Druey, Kirk M , Mandl, Judith N , Isidor, Bertrand , Ferreira, Carlos R , Freeman, Alexandra F , Karsak, Meliha , Mustillo, Peter J , Teo, Juliana , Chatron, Nicolas , Lecoquierre, Francois , Oler, Andrew J , Schmid, Jana Pachlopnik , Kuhns, Douglas B , Xu, Xuehua , Hauck, Fabian , Al-Herz, Waleed , Wagner, Matias , Terhal, Paulien A , Muurinen, Mari , Barlogis, Vincent , Loid, Petra , Keren, Boris , Pfundt, Rolph , Zarember, Kol A , Vill, Katharina , Olivier, Kenneth N , Lesca, Gaetan , Faivre, Laurence , Puel, Anne , Chou, Janet , Moutsopoulos, Niki M , Simons, Cas , Soldatos, Ariane , Masle-Farquhar, Etienne , Pittaluga, Stefania , Brink, Robert , Kong, Heidi H , Kabat, Juraj , Bierhals, Tatjana , Hsu, Amy P. , Gu, Jingwen , Trivellin, Giampaolo , Mazel, Benoît , Soomann, Maarja , Li, Samuel , Watts, Val J , Stratakis, Constantine A , Rodriguez-Quevedo, Maria F , Bruel, Ange-Line , Lipsanen-Nyman, Marita , Saultier, Paul , Lehalle, Daphne , Torres, Daniel , Barbarot, Sébastien , Neu, Axel , Similuk, Morgan N , McWalter, Kirsty , Blanc, Pierre , Bézieau, Stéphane , Geha, Raif S , Casanova, Jean Laurent , Makitie, Outi M , Edery, Patrick , Christodoulou, John , Germain, Ronald N , Goodnow, Christopher C , Sakmar, Thomas P , Billadeau, Daniel D , Kury, Sebastien , Katanaev, Vladimir L , Zhang, Yu , Lenardo, Michael J , Su, Helen C , Berchiche, Yamina A. , Wagner, Matias , Cruz, Phillip , Lesca, Gaëtan , Tusseau, Maud , Taft, Ryan J. , Pittaluga, Stefania , Baños-Piñero, Benito, Stratakis, Constantine A. , Jain, Rashmi, Bezieau, Stéphane , Jin, Tian , Kubisch, Christian , Küry, Sébastien , Su, Helen C.
Science | September 19, 2024 | Volume: 385 | Issue: 6715 | Pages: No page available
Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in GNAI2 , which encodes G αi2 , a key component in heterotrimeric G protein signal transduction usually thought to regulate adenylyl cyclase–mediated cyclic adenosine monophosphate (cAMP) production. Patients with activating G αi2 mutations had clinical presentations that included impaired immunity. Mutant G αi2 impaired cell migration and augmented responses to T cell receptor (TCR) stimulation. We found that mutant G αi2 influenced TCR signaling by sequestering the guanosine triphosphatase (GTPase)–activating protein RASA2, thereby promoting RAS activation and increasing downstream extracellular signal–regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)–AKT S6 signaling to drive cellular growth and proliferation.
TMEM161B regulates cerebral cortical gyration, Sonic Hedgehog signaling, and ciliary structure in the developing central nervous system
Akula, Shyam K. , Marciano, Jack H. , Lim, Youngshin , Exposito-Alonso, David , Hylton, Norma K. , Hwang, Grace H. , Neil, Jennifer E., Dominado, Nicole , Bunton-Stasyshyn, Rosie , Song, Janet , Talukdar, Maya , Schmid, Aloisia, Teboul, Lydia , Mo, Alisa , Finander, Benjamin , Beck, Samantha G., Yeh, Rebecca C., Otani, Aoi, Qian, Xuyu , DeGennaro, Ellen M. , Alkuraya, Fowzan S. , Maddirevula, Sateesh , Cascino, Gregory D. , Network, Undiagnosed Diseases, Burrage, Lindsay C. , Rosenfield, Jill A., Ketkar, Shamika , Clark, Gary, Bacino, Carlos A. , Lewis, Richard A. , Segal, Rosalind A. , Bazán, J. Fernando , Smith, K. A. , Golden, Jeffrey A. , Cho, Ginam , Walsh, Christopher A. , Alejandro, Mercedes E., Ashley, Euan A. , Baker, Eva H. , Balasubramanyam, Ashok , Barseghyan, Hayk , Batzli, Gabriel F., Bernstein, Jonathan A. , Bican, Anna, Bick, David , Birch, Camille L., Boone, Braden, Bostwick, Bret L. , Briere, Lauren C. , Brokamp, Elly , Brush, Matthew , Chen, Shan , Coakley, Terra R., Cobban, Laurel A., Colley, Heather A., Cooper, Cynthia M. , Craigen, William J., D’Souza, Precilla , Davids, Mariska, Davidson, Jean M. , Dayal, Jyoti G. , Dell’Angelica, Esteban C., Dhar, Shweta U. , Dipple, Katrina M. , Dorrani, Naghmeh, Dorset, Daniel C., Douglas, Jessica, Draper, David D., Dries, Annika M., Eckstein, David J. , Emrick, Lisa , Eng, Christine M. , Enns, Gregory M. , Eskin, Ascia , Esteves, Cecilia, Estwick, Tyra, Fernández, Liliana, Fogel, Brent L. , Friedman, Noah D., Gahl, William A. , Godfrey, Rena A., Goldstein, David B. , Gould, Sarah E., Groden, Catherine, Hamid, Rizwan , Hanchard, Neil A. , High, Frances A. , Hom, Jason , Howerton, Ellen M. , Jamal, Fariha , Jiang, Yong‐hui , Johnston, Jean M., Karaviti, Lefkothea , Kelley, Emily G., Koeller, David M. , Kohane, Isaac S. , Kohler, Jennefer N., Korrick, Susan , Kozuira, Mary, Krasnewich, Donna M., Krier, Joel B. , Lau, C. Christopher, Lazar, Jozef, LeBlanc, Kimberly , Lee, Brendan , Lee, Hane , Lewis, Richard A., Loscalzo, Joseph, Maas, Richard L., MacRae, Calum A. , Maduro, Valerie V. , Majcherska, Marta M., Malicdan, May Christine V. , Mamounas, Laura A., Manolio, Teri A. , Markello, Thomas C. , Martín, Martín G., Marwaha, Shruti , May, Thomas , McConkie‐Rosell, Allyn , McCormack, Colleen E., McCray, Alexa T. , Merker, Jason D. , Moretti, Paolo , Morimoto, Marie , Murdock, David R. , Muzny, Donna M., Nehrebecky, Michele, Nelson, Stan F., Newberry, J. Scott, Newman, John H. , Nicholas, Sarah K. , Novacic, Donna, Orengo, James P. , Pallais, J. Carl , Palmer, Christina G.S. , Papp, Jeanette C. , Parker, Neil H., Peña, Loren D.M. , Phillips, John A., Potocki, Lorraine , Pusey, Barbara N., Renteria, Genecee, Rives, Lynette, Robertson, Amy K., Rodan, Lance H. , Sampson, Jacinda B. , Samson, Susan L. , Schoch, Kelly, Shakachite, Lisa, Sharma, Prashant , Shashi, Vandana , Signer, Rebecca , Silverman, Edwin K. , Smith, Kevin S., Spillmann, Rebecca C. , Stoler, Joan M. , Sullivan, Jennifer A. , Tan, Queenie K.‐G., Tan, Wen-Haan, Toro, Camilo , Tran, Alyssa A., Urv, Tiina K. , Vogel, Tiphanie P. , Waggott, Daryl, Wahl, Colleen E., Walker, Melissa , Walley, Nicole M., Wan, Jijun , Ward, Patricia A., Westerfield, Monte, Wise, Anastasia L., Wolfe, Lynne A. , Yang, Yaping , Yoon, Amanda J., Yu, Guoyun, Zastrow, Diane B. , Zhao, Chunli , Zheng, Allison, Bunton-Stasyshyn, Rosie K , DeGennaro, Ellen M , Cascino, Gregory D , Giannini, Caterina , Burrage, Lindsay C , Rosenfield, Jill A , Bacino, Carlos , Lewis, Richard A , Segal, Rosalind A , Bazan, J Fernando , Smith, Kelly A , Golden, Jeffrey A , Cho, Ginam , Walsh, Christopher A , Alkuraya, Fowzan S , Akula, Shyam K , Shin, Taehwan , Giannini, Caterina , Network, Undiagnosed Diseases, Adams, David R. , Aday, Aaron W. , Allard, Patrick , Azamian, Mahshid S. , Beggs, Alan H. , Behnam, Babak , Bellen, Hugo J. , Berry, Gerard T. , Bonner, Devon E. , Brown, Donna M. , Burke, Elizabeth A. , Butte, Manish J. , Cogan, Joy D. , Cope, Heidi , D’Souza, Precilla , Douine, Emilie D. , Ferreira, Carlos R , Fieg, Elizabeth L. , Fisher, Paul Graham , Goldman, Alica M. , Gourdine, Jean-Philippe F. , Gropman, Andrea L , Haendel, Melissa , Holm, Ingrid A. , Huang, Yong , Jones, Angela , Kyle, Jennifer E , Lalani, Seema R , Levy, Shawn , Lewis, Richard A., Loo, Sandra K. , Macnamara, Ellen F. , Marom, Ronit , Martínez-Agosto, Julián A. , May, Thomas, Metz, Thomas , Might, Matthew , Mochida, Ganeshwaran H. , Mulvihill, John Joseph , Murphy, Jennifer L. , Muzny, Donna M. , Orange, Jordan S. , Phillips, John A., Posey, Jennifer E , Postlethwait, John H. , Reuter, Chloe M. , Rosenfeld, Jill A. , Scott, Daryl A , Sinsheimer, Janet S. , Stong, Nicholas , Sweetser, David A , Tifft, Cynthia , Vilain, Eric J. N. , Walley, Nicole M., Wangler, Michael F , Waters, Katrina M. , Webb‐Robertson, Bobbie‐Jo , Wheeler, Matthew T , Worthey, Elizabeth A. , Yamamoto, Shinya , Yang, John Jeongseok
Proceedings of the National Academy of Sciences | January 20, 2023 | Volume: 120 | Issue: 4 | Pages: No page available
Sonic hedgehog signaling regulates processes of embryonic development across multiple tissues, yet factors regulating context-specific Shh signaling remain poorly understood. Exome sequencing of families with polymicrogyria (disordered cortical folding) revealed multiple individuals with biallelic deleterious variants in TMEM161B , which encodes a multi-pass transmembrane protein of unknown function. Tmem161b null mice demonstrated holoprosencephaly, craniofacial midline defects, eye defects, and spinal cord patterning changes consistent with impaired Shh signaling, but were without limb defects, suggesting a CNS-specific role of Tmem161b. Tmem161b depletion impaired the response to Smoothened activation in vitro and disrupted cortical histogenesis in vivo in both mouse and ferret models, including leading to abnormal gyration in the ferret model. Tmem161b localizes non-exclusively to the primary cilium, and scanning electron microscopy revealed shortened, dysmorphic, and ballooned ventricular zone cilia in the Tmem161b null mouse, suggesting that the Shh-related phenotypes may reflect ciliary dysfunction. Our data identify TMEM161B as a regulator of cerebral cortical gyration, as involved in primary ciliary structure, as a regulator of Shh signaling, and further implicate Shh signaling in human gyral development.
Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer
Yan, Kezhi , Rousseau, Justine , Machol, Keren , Cross, Laura , Agre, Katherine , Gibson, Cynthia Forster, Goverde, Anne , Engleman, Kendra, Verdin, Hannah , Baere, Elfride De, Potocki, Lorraine , Zhou, Dihong , Cadieux‐Dion, Maxime , Wagner, Monisa, Hale, Rebecca J., Esber, Natacha , Solomon, Benjamin D. , Cho, Megan T. , Eyal, Roy , Hainlen, Meagan K., Mendelsohn, Bryce A. , Porter, Hillary M. , Lanpher, Brendan C. , Lewis, Andrea M. , Savatt, Juliann M. , Thiffault, Isabelle, Callewaert, Bert , Campeau, Philippe M. , Yang, Xiang‐Jiao , Agre, Katherine E, Esber, Natacha , Riley, Alan F , McWalter, Kirsty , Eyal, Roy , Mendelsohn, Bryce A , Thiffault, Isabelle , Callewaert, Bert , Campeau, Philippe M , Yang, Xiang-Jiao , Baere, Elfride De, Bellus, Gary A.
Science Advances | January 22, 2020 | Volume: 6 | Issue: 4 | Pages: No page available
Two lysine acyltransferases govern histone H3 propionylation at lysine 23 in normal and pathological conditions.