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作者：Brill, Julia; Clarke, Blaise; Hong, Ingie; Huganir, Richard L.
作者单位：Johns Hopkins University; Johns Hopkins University; Johns Hopkins University
摘要：SYNGAP1 is a key Ras-GAP protein enriched at excitatory synapses, with mutations causing intellectual disability and epilepsy in humans. Recent studies have revealed that in addition to its role as a negative regulator of G-protein signaling through its GAP enzymatic activity, SYNGAP1 plays an important structural role through its interaction with postsynaptic density proteins. Here, we reveal that intrinsic excitability deficits and seizure phenotypes in heterozygous Syngap1 knockout (KO) mic...
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作者：Dixon, Richard A.
作者单位：University of North Texas System; University of North Texas Denton; University of North Texas System; University of North Texas Denton
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作者：Faris, Shannon; Xia, Ke; Wagner, Andrew G.; Xu, Zihan; Smith, Nathan; Giner, Jose-Luis; Callahan, Brian; Xie, Jian; Wang, Chunyu
作者单位：Rensselaer Polytechnic Institute; Rensselaer Polytechnic Institute; State University of New York (SUNY) System; Binghamton University, SUNY; State University of New York (SUNY) System; State University of New York (SUNY) College of Environmental Science & Forestry; University of Nebraska System; University of Nebraska Medical Center
摘要：Hedgehog (Hh) signaling plays fundamental roles in embryonic development while its abnormal activation in adults is associated with cancer. Hh targeting drugs have gained FDA approval but resistance emerged quickly, underlining the need for novel types of Hh inhibitors. Hh signaling is initiated by the Hh ligand, generated from the autoprocessing of Hh precursor. However, the catalytic role of a highly conserved Hedgehog residue C143 is still poorly understood. Here, we confirmed that C143 is ...
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作者：Weeks, Amy M.
作者单位：University of Wisconsin System; University of Wisconsin Madison
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作者：Ambrogi, Marcela; Hernandez, Laura L.; Strand, Douglas W.; Kumar, Sathish; Romero, Michael F.; Barasch, Jonathan; Ridlon, Monica; Stietz, Kimberly P. Keil; Vezina, Chad M.
作者单位：University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; University of Texas System; University of Texas Southwestern Medical Center; Mayo Clinic; Columbia University
摘要：The urethra is considered a passive conduit for urine. Here, we reveal a surprising multicellular signaling pathway guiding the urethra's dynamic response to an invading pathogen. Using a genetic approach in female mice, we deposited uropathogenic Escherichia coli into the distal urethra to establish a model of ascending urinary tract infection that progresses to the bladder within 4 h. We show that urethral neuroendocrine cells (UNECs), and the serotonin they synthesize, protect the bladder f...
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作者：Sun, Shufeng; Liang, Biqing; Koplas, Adam; Tikhonenko, Irina; Nachury, Maxence; Khodjakov, Alexey; Sui, Haixin
作者单位：Wadsworth Center; State University of New York (SUNY) System; State University of New York (SUNY) System; University at Albany, SUNY; University of California System; University of California San Francisco
摘要：Structural homeostasis and proper distributions of signaling molecules in cilia require a constant flow of cargoes carried by intraflagellar transport (IFT) trains in both anterograde and retrograde directions within the thin, long ciliary shafts. In the motile cilium framework, the nine microtubule doublets of the same length serve as the transportation rails, and a preferential association to the two subtubules of the microtubule doublets prevents collisions among the IFT trains that move in...
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作者：Tworak, Aleksander; Smidak, Roman; Menezes, Carolline Rodrigues; Du, Samuel W.; Suh, Susie; Choi, Elliot H.; Imanishi, Sanae S.; Dong, Zhiqian; Lewandowski, Dominik; Fong, Kristen E.; Grigorean, Gabriela; Pinto, Antonio F. M.; Xu, Qianlan; Skowronska-Krawczyk, Dorota; Blackshaw, Seth; Imanishi, Yoshikazu; Palczewski, Krzysztof
作者单位：University of California System; University of California Irvine; University of California System; University of California Irvine; University of California System; University of California Irvine; University of California System; University of California Irvine; Indiana University System; Indiana University Bloomington; Indiana University System; Indiana University Bloomington; University of California System; University of California Davis; Salk Institute; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University
摘要：Membrane frizzled-related protein (MFRP), present in the retinal pigment epithelium (RPE), is an integral membrane protein essential for ocular development and the normal physiology of the retina. Mutations in MFRP are associated with autosomal recessive nonsyndromic nanophthalmos, leading to severe hyperopia and early-onset retinitis pigmentosa. While several preclinical gene-augmentation and gene-editing trials hold promise for future therapies aimed at stopping degeneration and restoring re...
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作者：Xiong, Rui; Hu, Yinyin; Wang, Menghan; Han, Ting; Hu, Yuying; Ma, Chaolin; Li, Baoming
作者单位：Nanchang University; Nanchang University; Hangzhou Normal University
摘要：Maternal separation (MS), a chronic stress event in early life, impairs myelination in the prefrontal cortex (PFC) and leads to PFC cognitive disorders. It remains largely unclear how such deficits are mediated. Here, we show that peripheral CD4+ T cells play an essential role in mediating the destructive effects of MS on medial prefrontal cortical (mPFC) myelination and cognitive functions in mice. Offspring mice with MS experience (MS mice) exhibited an increase in CD4+ T cells and xanthine ...
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作者：Li, Ming; Chen, Zhe; Guo, Zhengyang; Wang, Yang; Chai, Yongping; Li, Wei; Ou, Guangshuo
作者单位：Tsinghua University; Tsinghua University; Tsinghua University; Tsinghua University; Tsinghua University; Tsinghua University; Tsinghua University
摘要：The tubulin tail is a key element for microtubule (MT) functionality, but the functional redundancy of tubulin genes complicates the genetic determination of their physiological functions. Here, we removed the C-terminal tail of five alpha-and four beta-tubulin genes in the C. elegans genome. Sensory cilia typically exhibit an axoneme that longitudinally differentiates into a middle segment with doublet MTs and a distal segment with singlet MTs. However, the excision of the alpha-tubulin tail,...
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作者：Cheryan, Sapna; Muragishi, Gregg A.
作者单位：University of Washington; University of Washington Seattle
