Browsing by Author "Rehman, Atteeq U."

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    Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection
    (Springer Nature, 2019-02) Zhou, Wenjun; He, Yanlin; Rehman, Atteeq U.; Kong, Yan; Hong, Sungguan; Ding, Guolian; Yalamanchili, Hari Krishna; Wan, Ying-Wooi; Paul, Basil; Wang, Chuhan; Gong, Yingyun; Zhou, Wenxian; Liu, Hao; Dean, John; Scalais, Emmanuel; O’Driscoll, Mary; Morton, Jenny E.V.; Hou, Xinguo; Wu, Qi; Tong, Qingchun; Liu, Zhandong; Liu, Pengfei; Xu, Yong; Sun, Zheng; Biostatistics, IU School of Medicine
    Nuclear receptor corepressor 1 (NCOR1) and NCOR2 (also known as SMRT) regulate gene expression by activating histone deacetylase 3 through their deacetylase activation domain (DAD). We show that mice with DAD knock-in mutations have memory deficits, reduced anxiety levels, and reduced social interactions. Mice with NCOR1 and NORC2 depletion specifically in GABAergic neurons (NS-V mice) recapitulated the memory deficits and had reduced GABAA receptor subunit α2 (GABRA2) expression in lateral hypothalamus GABAergic (LHGABA) neurons. This was associated with LHGABA neuron hyperexcitability and impaired hippocampal long-term potentiation, through a monosynaptic LHGABA to CA3GABA projection. Optogenetic activation of this projection caused memory deficits, whereas targeted manipulation of LHGABA or CA3GABA neuron activity reversed memory deficits in NS-V mice. We describe de novo variants in NCOR1, NCOR2 or HDAC3 in patients with intellectual disability or neurodevelopmental disorders. These findings identify a hypothalamus-hippocampus projection that may link endocrine signals with synaptic plasticity through NCOR-mediated regulation of GABA signaling.
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    Taperin bundles F-actin at stereocilia pivot points enabling optimal lifelong mechanosensitivity
    (Rockefeller University Press, 2025) Belyantseva, Inna A.; Liu, Chang; Dragich, Abigail K.; Miyoshi, Takushi; Inagaki, Sayaka; Imtiaz, Ayesha; Tona, Risa; Zuluaga-Osorio, Karen Sofia; Hadi, Shadan; Wilson, Elizabeth; Morozko, Eva; Olszewski, Rafal; Yousaf, Rizwan; Sokolova, Yuliya; Riordan, Gavin P.; Aston, S. Andrew; Rehman, Atteeq U.; Fenollar Ferrer, Cristina; Wisniewski, Jan; Gu, Shoujun; Nayak, Gowri; Goodyear, Richard J.; Li, Jinan; Krey, Jocelyn F.; Wafa, Talah; Faridi, Rabia; Adadey, Samuel Mawuli; Drummond, Meghan; Perrin, Benjamin; Winkler, Dennis C.; Starost, Matthew F.; Cheng, Hui; Fitzgerald, Tracy; Richardson, Guy P.; Dong, Lijin; Barr-Gillespie, Peter G.; Hoa, Michael; Frolenkov, Gregory I.; Friedman, Thomas B.; Zhao, Bo; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Stereocilia are rod-like mechanosensory projections consisting of unidirectionally oriented actin filaments that extend into the inner ear hair cell cytoskeleton, forming dense rootlets. Taperin (TPRN) localizes to the narrowed-down base of stereocilia, where they pivot in response to sound and gravity. We show that TPRN-deficient mice have progressive deafness characterized by gradual asynchronous retraction and fusion of outer and inner hair cell stereocilia, followed by synaptic abnormalities. Stereocilia that lack TPRN develop warped rootlets with gradual loss of TRIOBP-5 and ANKRD24 from mechanosensory rows starting postnatally. In contrast, TPRN overexpression causes excessive F-actin bundling, extra rows, and over-elongation of stereocilia during development. Purified full-length mouse TPRN cross-links F-actin into bendable bundles reflecting in vivo data. This F-actin-bundling ability is attributed to the TPRN N-terminal region. TPRN interacts with the membrane receptor PTPRQ, connecting the F-actin core to the plasma membrane, stabilizing stereocilia. Thus, TPRN is a specialized F-actin bundler strategically located to augment stereocilia rootlet formation and their pivot point flexibility for sustained sound-induced deflections.