Journal article
Polarity of Neuronal Membrane Traffic Requires Sorting of Kinesin Motor Cargo during Entry into Dendrites by a Microtubule-Associated Septin
Developmental cell, v 46(2), pp 204-218
16 Jul 2018
PMID: 30016622
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Neuronal function requires axon-dendrite membrane polarity, which depends on sorting of membrane traffic during entry into axons. Due to a microtubule network of mixed polarity, dendrites receive vesicles from the cell body without apparent capacity for directional sorting. We found that, during entry into dendrites, axonally destined cargos move with a retrograde bias toward the cell body, while dendritically destined cargos are biased in the anterograde direction. A microtubule-associated septin (SEPT9), which localizes specifically in dendrites, impedes axonal cargo of kinesin-1/KIF5 and boosts kinesin-3/KIF1 motor cargo further into dendrites. In neurons and in vitro single-molecule motility assays, SEPT9 suppresses kinesin-1/KIF5 and enhances kinesin-3/KIF1 in a manner that depends on a lysine-rich loop of the kinesin motor domain. This differential regulation impacts partitioning of neuronal membrane proteins into axons-dendrites. Thus, polarized membrane traffic requires sorting during entry into dendrites by a septin-mediated mechanism that bestows directional bias on microtubules of mixed orientation.
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•Kinesin motor cargos enter dendrites with differential motility and directional bias•SEPT9 is a dendritic MAP that impedes movement of kinesin-1/KIF5 and axonal cargo•SEPT9 promotes anterograde movement of kinesin-3/KIF1A and its dendritic cargo•SEPT9 distinguishes between loops L12 of KIF5 and KIF1A for entry into dendrites
Polarized neuronal membrane traffic relies primarily on sorting at axonal entry, while dendrites appear to lack directional sorting due to mixed microtubule orientation. Karasmanis et al. show that a dendritically enriched microtubule-associated septin, SEPT9, impedes axonal kinesin-1/KIF5 but promotes dendritic kinesin-3/KIF1A motor cargo, thereby bestowing directional bias during dendritic entry.
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Details
- Title
- Polarity of Neuronal Membrane Traffic Requires Sorting of Kinesin Motor Cargo during Entry into Dendrites by a Microtubule-Associated Septin
- Creators
- Eva P Karasmanis - Department of Biology, Drexel University, Philadelphia, PA 19104, USACat-Thi Phan - Department of Biology, Drexel University, Philadelphia, PA 19104, USADimitrios Angelis - Department of Biology, Drexel University, Philadelphia, PA 19104, USAIlona A Kesisova - Department of Biology, Drexel University, Philadelphia, PA 19104, USACasper C Hoogenraad - Cell Biology, Department of Biology, Utrecht University, Utrecht 3584 CH, the NetherlandsRichard J McKenney - Department of Molecular and Cellular Biology, University of California Davis, Davis, CA 95616, USAElias T Spiliotis - Department of Biology, Drexel University, Philadelphia, PA 19104, USA
- Publication Details
- Developmental cell, v 46(2), pp 204-218
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; Pediatrics
- Web of Science ID
- WOS:000438893000010
- Scopus ID
- 2-s2.0-85049356151
- Other Identifier
- 991014878172004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology
- Developmental Biology