Polarity of Neuronal Membrane Traffic Requires Sorting of Kinesin Motor Cargo during Entry into Dendrites by a Microtubule-Associated Septin

Eva P. Karasmanis, Cat Thi Phan, Dimitrios Angelis, Ilona A. Kesisova, Casper C. Hoogenraad, Richard Mckenney, Elias T. Spiliotis

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)204-218.e7
JournalDevelopmental Cell
Volume46
Issue number2
DOIs
StatePublished - Jul 16 2018

Keywords

  • dendrites
  • dendritic sorting
  • kinesins
  • membrane traffic
  • microtubule motors
  • microtubule-associated proteins
  • microtubules
  • neuronal polarity
  • neuronal trafficking
  • septins

ASJC Scopus subject areas

  • Developmental Biology

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