The densely ciliated granule cell layer of the adult murine hippocampal dentate gyrus is one of two sites of adult neurogenesis. The granule cells have already been proven to localize their SSTR3 (somatostatin receptor 3) receptors to their so-called primary cilia. Here we show for the first time that 70-90% of these cells in 7-18 months-old wild-type and 3×Tg-AD (Alzheimer disease transgenic) mice also load p75(NTR) receptors into the structures containing SSTR3, i.e., their primary cilia. On the other hand, p75(NTR')s TrkA co-receptors were not localized to cilia but conventionally distributed throughout the cell surface. Significantly fewer cells (20-40%) in the hippocampal CA1 and CA3 regions and cerebral cortex have p75(NTR) containing cilia. While we don't know what the impact of the cilial localization of p75(NTR) on dentate gyral adult neurogenesis and memory encoding might be, the cilia's amyloid β-activatable p75(NTR) receptors could be damaging or lethal to the hippocampal functioning of amyloid β-accumulating Alzheimer brain.
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http://dx.doi.org/10.1016/j.bbrc.2010.09.081 | DOI Listing |
Am J Hum Genet
December 2024
Laboratory of Human Genetics & Therapeutics, Genome Institute of Singapore (GIS), A(∗)STAR, Singapore, Singapore; Laboratory of Human Genetics & Therapeutics, BESE, KAUST, Thuwal, Saudi Arabia; Department of Physiology, Cardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address:
Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Case Western Reserve University, Cleveland, OH, USA.
Background: Emerging evidence links Alzheimer's disease (AD) to dysfunction of the primary cilium, a historically overlooked organelle that serves as the neuron's antenna. All neurons harbor a single primary cilium that projects from the membrane to sense changes in the extracellular environment. Primary cilia dysfunction leads to a group of diseases called 'ciliopathies', which are associated with reduced hippocampal and cortical mass, as well as neurocognitive impairment.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Toledo/College of Pharmacy, Toledo, OH, USA.
Background: Primary cilia are solitary membrane-bound organelles emanating from the apical surface of most mammalian cells. They serve as sensory organelles sampling the extracellular environment and reprogramming the transcriptional machinery in response to changes in fluid flow. Ciliopathies, a group of genetic disorders characterized by disrupted cilia structure and/or function, share common phenotypes such as vascular dysfunction and cognitive impairment.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Molecular, Cellular, and Biomedical Sciences, College of Life Sciences and Agriculture, University of New Hampshire, Durham, NH, 03824, USA.
The primary cilium is a hair-like organelle that hosts molecular machinery for various developmental and homeostatic signaling pathways. Its alteration can cause rare ciliopathies such as the Bardet-Biedl and Joubert syndromes, but is also linked to Alzheimer's disease, clinical depression, and autism spectrum disorder. These afflictions are caused by disturbances in a wide variety of genes but a common phenotype amongst them is cognitive impairment.
View Article and Find Full Text PDFNat Commun
January 2025
Laboratory of Developmental Genetics, The Rockefeller University, New York, NY, USA.
Glia assess axon structure to modulate myelination and axon repair. Whether glia similarly detect dendrites and their substructures is not well understood. Here we show that glia monitor the integrity of dendrite substructures and transiently protect them against perturbations.
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