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

Maniar TA, Kaplan M, Wang GJ, Shen K, Wei L, Shaw JE, Koushika SP, Bargmann CI - Nat. Neurosci. (2011)

Bottom Line: The causative relationships among 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.We suggest that UNC-44 and UNC-33 direct polarized sorting through their global effects on neuronal microtubule organization.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neural Circuits and Behavior, Howard Hughes Medical Institute, The Rockefeller University, New York, New York, USA.

ABSTRACT
The polarized distribution of neuronal proteins to axons and dendrites relies on microtubule-binding proteins such as CRMP, directed motors such as the kinesin UNC-104 (Kif1A) and diffusion barriers such as ankyrin. The causative relationships among 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 were mislocalized to dendrites and vice versa, suggesting bidirectional failures of axon-dendrite identity. unc-44 directed UNC-33 localization to axons, where it was enriched in a region that resembled the axon initial segment. unc-33 and unc-44 were both required to establish the asymmetric dynamics of axonal and dendritic microtubules; in their absence, microtubules were disorganized, the axonal kinesin UNC-104 invaded dendrites, and inappropriate UNC-104 activity randomized axonal protein sorting. We suggest that UNC-44 and UNC-33 direct polarized sorting through their global effects on neuronal microtubule organization.

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A sensory chemoreceptor protein is mislocalized to axons in unc-33 mutants(a) Schematic diagram of AWB chemosensory neurons in the head. (b) Representative maximum projection fluorescence images showing ODR-10::GFP localization in AWB neurons of wild type, unc-33, unc-104, and unc-104; unc-33 double mutant animals. Yellow arrowheads indicate ODR-10::GFP in axons. Anterior is at left and dorsal is up in all images. Scale bar, 10 μm.(c,d) Quantification of animals with ODR-10::GFP fluorescence in axons (n>30 animals per genotype). Error bars indicate s.e.p.
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Figure 6: A sensory chemoreceptor protein is mislocalized to axons in unc-33 mutants(a) Schematic diagram of AWB chemosensory neurons in the head. (b) Representative maximum projection fluorescence images showing ODR-10::GFP localization in AWB neurons of wild type, unc-33, unc-104, and unc-104; unc-33 double mutant animals. Yellow arrowheads indicate ODR-10::GFP in axons. Anterior is at left and dorsal is up in all images. Scale bar, 10 μm.(c,d) Quantification of animals with ODR-10::GFP fluorescence in axons (n>30 animals per genotype). Error bars indicate s.e.p.

Mentions: To ask whether unc-33 affected sorting of dendritic proteins as well as axonal proteins, we examined the AWB chemosensory neuron, which has a dendrite that terminates in an anterior sensory cilium and an axon that grows into the nerve ring (Fig. 6a). ODR-10::GFP, a chemosensory G protein-coupled receptor, is enriched in AWB cilia and excluded from axons of wild-type animals37 (Fig. 6b). In unc-33 mutants, however, ODR-10::GFP was present in AWB axons as well as AWB cilia (Fig. 6b). The defect in ODR-10::GFP localization in unc-33 mutants was not as severe as the defect in axon protein localization, but it was consistently observed in multiple unc-33 alleles at both early and late larval stages (Fig. 6c).


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

Maniar TA, Kaplan M, Wang GJ, Shen K, Wei L, Shaw JE, Koushika SP, Bargmann CI - Nat. Neurosci. (2011)

A sensory chemoreceptor protein is mislocalized to axons in unc-33 mutants(a) Schematic diagram of AWB chemosensory neurons in the head. (b) Representative maximum projection fluorescence images showing ODR-10::GFP localization in AWB neurons of wild type, unc-33, unc-104, and unc-104; unc-33 double mutant animals. Yellow arrowheads indicate ODR-10::GFP in axons. Anterior is at left and dorsal is up in all images. Scale bar, 10 μm.(c,d) Quantification of animals with ODR-10::GFP fluorescence in axons (n>30 animals per genotype). Error bars indicate s.e.p.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4328884&req=5

Figure 6: A sensory chemoreceptor protein is mislocalized to axons in unc-33 mutants(a) Schematic diagram of AWB chemosensory neurons in the head. (b) Representative maximum projection fluorescence images showing ODR-10::GFP localization in AWB neurons of wild type, unc-33, unc-104, and unc-104; unc-33 double mutant animals. Yellow arrowheads indicate ODR-10::GFP in axons. Anterior is at left and dorsal is up in all images. Scale bar, 10 μm.(c,d) Quantification of animals with ODR-10::GFP fluorescence in axons (n>30 animals per genotype). Error bars indicate s.e.p.
Mentions: To ask whether unc-33 affected sorting of dendritic proteins as well as axonal proteins, we examined the AWB chemosensory neuron, which has a dendrite that terminates in an anterior sensory cilium and an axon that grows into the nerve ring (Fig. 6a). ODR-10::GFP, a chemosensory G protein-coupled receptor, is enriched in AWB cilia and excluded from axons of wild-type animals37 (Fig. 6b). In unc-33 mutants, however, ODR-10::GFP was present in AWB axons as well as AWB cilia (Fig. 6b). The defect in ODR-10::GFP localization in unc-33 mutants was not as severe as the defect in axon protein localization, but it was consistently observed in multiple unc-33 alleles at both early and late larval stages (Fig. 6c).

Bottom Line: The causative relationships among 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.We suggest that UNC-44 and UNC-33 direct polarized sorting through their global effects on neuronal microtubule organization.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neural Circuits and Behavior, Howard Hughes Medical Institute, The Rockefeller University, New York, New York, USA.

ABSTRACT
The polarized distribution of neuronal proteins to axons and dendrites relies on microtubule-binding proteins such as CRMP, directed motors such as the kinesin UNC-104 (Kif1A) and diffusion barriers such as ankyrin. The causative relationships among 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 were mislocalized to dendrites and vice versa, suggesting bidirectional failures of axon-dendrite identity. unc-44 directed UNC-33 localization to axons, where it was enriched in a region that resembled the axon initial segment. unc-33 and unc-44 were both required to establish the asymmetric dynamics of axonal and dendritic microtubules; in their absence, microtubules were disorganized, the axonal kinesin UNC-104 invaded dendrites, and inappropriate UNC-104 activity randomized axonal protein sorting. We suggest that UNC-44 and UNC-33 direct polarized sorting through their global effects on neuronal microtubule organization.

Show MeSH
Related in: MedlinePlus