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Intracellular transport involves the regulation of microtubule motor interactions with cargo, but the underlying mechanisms are not well understood. Septins are membrane- and microtubule-binding proteins that assemble into filamentous, scaffold-like structures. Septins are implicated in microtubule-dependent transport, but their roles are unknown. Here we describe a novel interaction between KIF17, a kinesin 2 family motor, and septin 9 (SEPT9). We show that SEPT9 associates directly with the C-terminal tail of KIF17 and interacts preferentially with the extended cargo-binding conformation of KIF17. In developing rat hippocampal neurons, SEPT9 partially colocalizes and comigrates with KIF17. We show that SEPT9 interacts with the KIF17 tail domain that associates with mLin-10/Mint1, a cargo adaptor/scaffold protein, which underlies the mechanism of KIF17 binding to the NMDA receptor subunit 2B (NR2B). Significantly, SEPT9 interferes with binding of the PDZ1 domain of mLin-10/Mint1 to KIF17 and thereby down-regulates NR2B transport into the dendrites of hippocampal neurons. Measurements of KIF17 motility in live neurons show that SEPT9 does not affect the microtubule-dependent motility of KIF17. These results provide the first evidence of an interaction between septins and a nonmitotic kinesin and suggest that SEPT9 modulates the interactions of KIF17 with membrane cargo.
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http://dx.doi.org/10.1091/mbc.E15-07-0493 | DOI Listing |
Brain
October 2024
Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Speech and language disorders are known to have a substantial genetic contribution. Although frequently examined as components of other conditions, research on the genetic basis of linguistic differences as separate phenotypic subgroups has been limited so far. Here, we performed an in-depth characterization of speech and language disorders in 52 143 individuals, reconstructing clinical histories using a large-scale data-mining approach of the electronic medical records from an entire large paediatric healthcare network.
View Article and Find Full Text PDFSchizophrenia (Heidelb)
October 2024
Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Methamphetamine use can produce psychotic symptoms almost indistinguishable from schizophrenia (SCZ). Variation in DNA methylation may be closely implicated in the etiology and longitudinal development of psychiatric disorders. However, the relationship between psychotic symptoms, functional disability, and DNA methylation is still unclear.
View Article and Find Full Text PDFSLAS Technol
October 2024
Institute of Neuroscience and Guangxi Key Laboratory of Brain Science, Department of Human Anatomy, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China; Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Health Commission Key Laboratory of Basic Research on Brain Function and Disease, Nanning, Guangxi, China; China-ASEAN Research Center for Innovation and Development in Brain Science, Nanning, Guangxi, China; Guangxi Key Laboratory of Regenerative Medicine, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Nanning, Guangxi, China. Electronic address:
Breast cancer (BC), a prevalent and severe malignancy, detrimentally affects women globally. Its prognostic implications are profoundly influenced by gene expression patterns. This study retrieved 509 BCE-associated oncogenes and 1,012 neurotransmitter receptor-related genes from the GSEA and KEGG databases, intersecting to identify 98 relevant genes.
View Article and Find Full Text PDFBMB Rep
October 2024
Department of Biochemistry, College of Medicine, Inje University, Busan 47392; Demetia and Neurodegenerative Disease Research Center, College of Medicine, Inje University, Busan 47392, Korea.
The heterotrimeric molecular motor kinesin-2 is involved in the microtubule-dependent transport of intracellular cargo. It consists of two distinct motor subunits (KIF3A, and KIF3B) and a non-motor subunit, kinesin-associated protein 3 (KAP3). The cargo-binding domain (CBD) at the carboxyl (C)-terminus of KIF3s plays an important role in the interaction with several different binding proteins.
View Article and Find Full Text PDFSci Adv
April 2024
Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
While the kinesin-2 motors KIF3A and KIF3B have essential roles in ciliogenesis and Hedgehog (HH) signal transduction, potential role(s) for another kinesin-2 motor, KIF17, in HH signaling have yet to be explored. Here, we investigated the contribution of KIF17 to HH-dependent cerebellar development, where is expressed in both HH-producing Purkinje cells and HH-responding cerebellar granule neuron progenitors (CGNPs). Germline deletion in mice results in cerebellar hypoplasia due to reduced CGNP proliferation, a consequence of decreased HH pathway activity mediated through decreased Sonic HH (SHH) protein.
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