We identified a direct interaction between the neuronal transmembrane protein calsyntenin-1 and the light chain of Kinesin-1 (KLC1). GST pulldowns demonstrated that two highly conserved segments in the cytoplasmic domain of calsyntenin-1 mediate binding to the tetratricopeptide repeats of KLC1. A complex containing calsyntenin-1 and the Kinesin-1 motor was isolated from developing mouse brain and immunoelectron microscopy located calsyntenin-1 in association with tubulovesicular organelles in axonal fiber tracts. In primary neuronal cultures, calsyntenin-1-containing organelles were aligned along microtubules and partially colocalized with Kinesin-1. Using live imaging, we showed that these organelles are transported along axons with a velocity and processivity typical for fast axonal transport. Point mutations in the two kinesin-binding segments of calsyntenin-1 significantly reduced binding to KLC1 in vitro, and vesicles bearing mutated calsyntenin-1 exhibited a markedly altered anterograde axonal transport. In summary, our results indicate that calsyntenin-1 links a certain type of vesicular and tubulovesicular organelles to the Kinesin-1 motor.
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http://dx.doi.org/10.1091/mbc.e06-02-0112 | DOI Listing |
Synapse
September 2024
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Int J Mol Sci
July 2024
Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy.
Alzheimer's disease (AD) and Frontotemporal lobar degeneration (FTLD) represent the most common forms of neurodegenerative dementias with a highly phenotypic variability. Herein, we investigated the role of genetic variants related to the immune system and inflammation as genetic modulators in AD and related dementias. In patients with sporadic AD/FTLD (n = 300) and / mutation carriers (n = 80), we performed a targeted sequencing of 50 genes belonging to the immune system and inflammation, selected based on their high expression in brain regions and low tolerance to genetic variation.
View Article and Find Full Text PDFJ Neuroinflammation
December 2022
Department of Neuroscience, Monash University, Melbourne, VIC, Australia.
The pathophysiology of traumatic brain injury (TBI) requires further characterization to fully elucidate changes in molecular pathways. Cerebrospinal fluid (CSF) provides a rich repository of brain-associated proteins. In this retrospective observational study, we implemented high-resolution mass spectrometry to evaluate changes to the CSF proteome after severe TBI.
View Article and Find Full Text PDFCardiovasc Drugs Ther
April 2024
Medical Big Data Research Center, Chinese PLA General Hospital, Beijing, 100853, China.
Purpose: Doxorubicin is an important cancer chemotherapeutic agent with severe cardiotoxic effects that eventually lead to dilated cardiomyopathy (DCM). Calsyntenin-1(CLSTN1) plays a critical role in the nervous system, but its relevance in cardiovascular diseases is unknown. We investigated the significance of CLSTN1 in doxorubicin-induced DCM.
View Article and Find Full Text PDFMol Neurodegener
April 2022
Hospital de La Santa Creu I Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
Background: Synapse degeneration is an early event in pathological frontotemporal lobar degeneration (FTLD). Consequently, a surrogate marker of synapse loss could be used to monitor early pathologic changes in patients with underlying FTLD. The aim of this study was to evaluate the relationship of antemortem cerebrospinal fluid (CSF) levels of 8 synaptic proteins with postmortem global tau and TDP-43 burden and cognitive performance and to assess their diagnostic capacity in a neuropathological FTLD cohort.
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