DYNLRB1 is Essential for Dynein Mediated Transport and Neuronal Survival

Abstract

The cytoplasmic dynein motor complex transports essential signals and organelles from the cell periphery to perinuclear region, hence is critical for the survival and function of highly polarized cells such as neurons. Dynein Light Chain Roadblock-Type 1 (DYNLRB1) is thought to be an accessory subunit required for specific cargos, but here we show that it is essential for general dynein-mediated transport and sensory neuron survival. Homozygous Dynlrb1 null mice are not viable and die during early embryonic development. Furthermore, heterozygous or adult knockdown animals display reduced neuronal growth, and selective depletion of Dynlrb1 in proprioceptive neurons compromises their survival. Conditional depletion of Dynlrb1 in sensory neurons causes deficits in several signaling pathways, including β-catenin subcellular localization, and a severe impairment in the axonal transport of both lysosomes and retrograde signaling endosomes. Hence, DYNLRB1 is an essential component of the dynein complex.

Analysis of multi‐omics data on the relationship between epigenetic changes and nervous system disorders caused by exposure to environmentally harmful substances

“…We confirmed that six of the genes targeted by the miR‐15 family were significantly downregulated and had a negative effect on the nervous system. In particular, downregulated expression of ABL2 (also called ARG) and DYNC1LI2 impairs the stability of the dendritic spine and arbor and reduces axonal outgrowth 27,30 . Meanwhile, ATXN2 downregulation may induce motor hyperactivity 28 .…”

A conditional null allele of Dync1h1 enables targeted analyses of dynein roles in neuronal length sensing and neurological disorders

“…Catwalk: the test was carried on as previously described (Terenzio et al, 2020). Motivation was achieved by placing the home cage at the runway end and each mouse was tested 3-5 times.…”