UNC-33 (CRMP) and ankyrin organize microtubules and localize kinesin to polarize axon-dendrite sorting

Abstract

The polarized distribution of neuronal proteins to axons and dendrites relies upon microtubule-binding proteins such as CRMP, directed motors such as kinesin UNC-104/Kif1A, and diffusion barriers such as ankyrin. The causative relationships between these molecules are unknown. We show here that Caenorhabditis elegans CRMP (UNC-33) acts early in neuronal development, together with ankyrin (UNC-44), to organize microtubule asymmetry and axon-dendrite sorting. In unc-33 and unc-44 mutants, axonal proteins are present in dendrites and vice versa, suggesting bidirectional failures of axon-dendrite identity. UNC-33 protein is localized to axons by unc-44, and enriched in a region that resembles the axon initial segment. unc-33 and unc-44 establish the asymmetric dynamics of axonal and dendritic microtubules; in their absence, microtubules are disorganized, the axonal kinesin UNC-104 invades dendrites, and inappropriate UNC-104 activity randomizes axonal protein sorting. We suggest that UNC-44 and UNC-33 direct polarized sorting through their global effects on neuronal microtubule organization.

Synapse-Assembly Proteins Maintain Synaptic Vesicle Cluster Stability and Regulate Synaptic Vesicle Transport in Caenorhabditis elegans

“…In C. elegans neurons, including cholinergic motor neurons, microtubules in the axon are oriented with their plus ends out (i.e., toward the synaptic region), whereas microtubules in the dendrite are predominantly oriented with their minus ends out (Goodwin et al 2012;Maniar et al 2012;Yan et al 2013). found that eliminating the cyclindependent kinase pathways CDK-5 (cyclin-dependent kinase 5) and PCT-1 (Pctaire kinase) in the DA9 motor neuron causes a redistribution of SVs from the synaptic region to the cell soma and dendrite similar to unc-104 loss-of-function mutants and that this redistribution requires components of the dynein minus-end-directed motor complex, such as DHC-1 (dynein heavy chain) and NUD-2 (known as NUDEL in vertebrates).…”

Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to mediate Sema3A signalling

“…The mild phenotype in fln-1(tm545) mutant may be due to the limited contribution of FLN-1 in DD/VD projection and/or the compensation by the other filamin isoform in C. elegans, FLN-2. The severe abnormal phenotype in unc-33 mutants may reflect the insufficient regulation of tubulin assembly 6 and/or the polarized defect 8 . fln-1(tm545) enhanced the phenotype of weak allele mutant unc-33(e204) (Fig.…”

“…CRMPs share significant homology with UNC-33 in Caenorhabditis elegans 5 . UNC-33 is involved in the axonal outgrowth and guidance of various neurons through the regulation of tubulin dynamics and neuronal polarity in nematodes [6][7][8] .…”

AFF-1 fusogen can rejuvenate the regenerative potential of adult dendritic trees via self-fusion

“…1A) (Oren-Suissa et al, 2010). These dendritic trees arise and are dynamically maintained through several intrinsic and extrinsic genetic pathways (Chatzigeorgiou et al, 2010;Cohen et al, 2014;Dong et al, 2013Dong et al, , 2015Husson et al, 2012;Liu and Shen, 2011;Maniar et al, 2012;Oren-Suissa et al, 2010;Salzberg et al, 2013;Smith et al, 2010;Wei et al, 2015).…”