RGD Reference Report - MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- versus KIF5-Dependent Cargo Transport in Sensory Neurons. - Rat Genome Database

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MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- versus KIF5-Dependent Cargo Transport in Sensory Neurons.

Authors: Gumy, Laura F  Katrukha, Eugene A  Grigoriev, Ilya  Jaarsma, Dick  Kapitein, Lukas C  Akhmanova, Anna  Hoogenraad, Casper C 
Citation: Gumy LF, etal., Neuron. 2017 Apr 19;94(2):347-362.e7. doi: 10.1016/j.neuron.2017.03.046.
RGD ID: 13514087
Pubmed: PMID:28426968   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuron.2017.03.046   (Journal Full-text)

Polarized cargo transport is essential for neuronal function. However, the minimal basic components required for selective cargo sorting and distribution in neurons remain elusive. We found that in sensory neurons the axon initial segment is largely absent and that microtubule-associated protein 2 (MAP2) defines the cargo-filtering zone in the proximal axon. Here, MAP2 directs axonal cargo entry by coordinating the activities of molecular motors. We show that distinct kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport. MAP2 inhibits "slow" kinesin-1 motor activity and allows kinesin-3 to drive robust cargo transport from the soma into the axon. In the distal axon, the inhibitory action of MAP2 decreases, leading to regained kinesin-1 activity and vesicle distribution. We propose that selective axonal cargo trafficking requires the MAP2-defined pre-axonal filtering zone and the ability of cargos to switch between distinct kinesin motor activities.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kif1aRatanterograde neuronal dense core vesicle transport involved_inIGIUniProtKB:O35787 and UniProtKB:O88658PMID:28426968ARUK-UCL 
Kif1bRatanterograde neuronal dense core vesicle transport involved_inIGIUniProtKB:F1M4A4 and UniProtKB:O35787PMID:28426968ARUK-UCL 
Kif1cRatanterograde neuronal dense core vesicle transport involved_inIGIUniProtKB:F1M4A4 and UniProtKB:O88658PMID:28426968ARUK-UCL 
Map2Ratnegative regulation of axon extension involved_inIMP PMID:28426968ARUK-UCL 
Trim46Ratnegative regulation of axon extension involved_inIMP PMID:28426968ARUK-UCL 
Map2Ratnegative regulation of microtubule polymerization involved_inIMP PMID:28426968ARUK-UCL 
Map2Ratpositive regulation of anterograde dense core granule transport involved_inIMP PMID:28426968ARUK-UCL 
Trim46Ratpositive regulation of anterograde dense core granule transport involved_inIMP PMID:28426968ARUK-UCL 
Map2Ratpositive regulation of anterograde synaptic vesicle transport involved_inIMP PMID:28426968ARUK-UCL 
Map2Ratregulation of organelle transport along microtubule involved_inIMP PMID:28426968ARUK-UCL 
Map2Ratregulation of protein localization involved_inIMP PMID:28426968ARUK-UCL 
Trim46Ratregulation of protein localization involved_inIMP PMID:28426968ARUK-UCL 
Kif1aRatretrograde neuronal dense core vesicle transport involved_inIGIUniProtKB:O35787 and UniProtKB:O88658PMID:28426968ARUK-UCL 
Kif1bRatretrograde neuronal dense core vesicle transport involved_inIGIUniProtKB:F1M4A4 and UniProtKB:O35787PMID:28426968ARUK-UCL 
Kif1cRatretrograde neuronal dense core vesicle transport involved_inIGIUniProtKB:F1M4A4 and UniProtKB:O88658PMID:28426968ARUK-UCL 
Kif5aRatretrograde neuronal dense core vesicle transport involved_inIGIUniProtKB:Q2PQA9PMID:28426968ARUK-UCL 
Kif5bRatretrograde neuronal dense core vesicle transport involved_inIGIUniProtKB:Q6QLM7PMID:28426968ARUK-UCL 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Map1aRataxon located_inIDA PMID:28426968ARUK-UCL 
Map1bRataxon located_inIDA PMID:28426968ARUK-UCL 
Map4Rataxon located_inIDA PMID:28426968ARUK-UCL 
Map7Rataxon located_inIDA PMID:28426968ARUK-UCL 
Map9Rataxon located_inIDA PMID:28426968ARUK-UCL 
Map2Rataxon hillock located_inIDA PMID:28426968ARUK-UCL 
Ank3Rataxon initial segment located_inIDA PMID:28426968ARUK-UCL 
Map2Rataxon initial segment located_inIDA PMID:28426968ARUK-UCL 
NfascRataxon initial segment located_inIDA PMID:28426968ARUK-UCL 
Sptbn4Rataxon initial segment located_inIDA PMID:28426968ARUK-UCL 
Trim46Ratmain axon located_inIDA PMID:28426968ARUK-UCL 
Map2Ratneuronal cell body located_inIDA PMID:28426968ARUK-UCL 
Ank3Ratnode of Ranvier located_inIDA PMID:28426968ARUK-UCL 
Map2Ratproximal neuron projection located_inIDA PMID:28426968ARUK-UCL 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Map2Ratprotein binding enablesIPIUniProtKB:P33176PMID:28426968ARUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Ank3  (ankyrin 3)
Kif1a  (kinesin family member 1A)
Kif1b  (kinesin family member 1B)
Kif1c  (kinesin family member 1C)
Kif5a  (kinesin family member 5A)
Kif5b  (kinesin family member 5B)
Map1a  (microtubule-associated protein 1A)
Map1b  (microtubule-associated protein 1B)
Map2  (microtubule-associated protein 2)
Map4  (microtubule-associated protein 4)
Map7  (microtubule-associated protein 7)
Map9  (microtubule-associated protein 9)
Nfasc  (neurofascin)
Sptbn4  (spectrin, beta, non-erythrocytic 4)
Trim46  (tripartite motif-containing 46)


Additional Information