Kif1B interacts with KBP to promote axon elongation by localizing a microtubule regulator to growth cones

Catherine M. Drerup, Sarah Lusk, Alex Nechiporuk

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Delivery of proteins and organelles to the growth cone during axon extension relies on anterograde transport by kinesin motors. Though critical for neural circuit development, the mechanisms of cargo-specific anterograde transport during axon extension are only starting to be explored. Cargos of particular importance for axon outgrowth are microtubule modifiers, such as SCG10 (Stathmin-2). SCG10 is expressed solely during axon extension, localized to growth cones, and essential for axon outgrowth; however, the mechanisms of SCG10 transport and activity were still debated. Using zebrafish mutants and in vivo imaging, we identified the Kif1B motor and its interactor Kif1 binding protein (KBP) as critical for SCG10 transport to axon growth cones and complete axon extension. Axon truncation in kbpst23 mutants can be suppressed by SCG10 overexpression, confirming the direct relationship between decreased SCG10 levels and failed axon outgrowth. Live imaging revealed that the reduced levels of SCG10 in kbpst23 mutant growth cones led to altered microtubule stability, defining the mechanistic basis of axon truncation. Thus, our data reveal a novel role for the Kif1B-KBP complex in the anterograde transport of SCG10, which is necessary for proper microtubule dynamics and subsequent axon extension.

Original languageEnglish (US)
Pages (from-to)7014-7026
Number of pages13
JournalJournal of Neuroscience
Volume36
Issue number26
DOIs
StatePublished - Jun 29 2016

Fingerprint

Growth Cones
Microtubules
Axons
Carrier Proteins
Stathmin
Kinesin
Zebrafish
Organelles

Keywords

  • Axon extension
  • KBP
  • KIF1B
  • SCG10
  • Stathmin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kif1B interacts with KBP to promote axon elongation by localizing a microtubule regulator to growth cones. / Drerup, Catherine M.; Lusk, Sarah; Nechiporuk, Alex.

In: Journal of Neuroscience, Vol. 36, No. 26, 29.06.2016, p. 7014-7026.

Research output: Contribution to journalArticle

@article{0b9b4928a34841669ef1316e04d0b8b7,
title = "Kif1B interacts with KBP to promote axon elongation by localizing a microtubule regulator to growth cones",
abstract = "Delivery of proteins and organelles to the growth cone during axon extension relies on anterograde transport by kinesin motors. Though critical for neural circuit development, the mechanisms of cargo-specific anterograde transport during axon extension are only starting to be explored. Cargos of particular importance for axon outgrowth are microtubule modifiers, such as SCG10 (Stathmin-2). SCG10 is expressed solely during axon extension, localized to growth cones, and essential for axon outgrowth; however, the mechanisms of SCG10 transport and activity were still debated. Using zebrafish mutants and in vivo imaging, we identified the Kif1B motor and its interactor Kif1 binding protein (KBP) as critical for SCG10 transport to axon growth cones and complete axon extension. Axon truncation in kbpst23 mutants can be suppressed by SCG10 overexpression, confirming the direct relationship between decreased SCG10 levels and failed axon outgrowth. Live imaging revealed that the reduced levels of SCG10 in kbpst23 mutant growth cones led to altered microtubule stability, defining the mechanistic basis of axon truncation. Thus, our data reveal a novel role for the Kif1B-KBP complex in the anterograde transport of SCG10, which is necessary for proper microtubule dynamics and subsequent axon extension.",
keywords = "Axon extension, KBP, KIF1B, SCG10, Stathmin",
author = "Drerup, {Catherine M.} and Sarah Lusk and Alex Nechiporuk",
year = "2016",
month = "6",
day = "29",
doi = "10.1523/JNEUROSCI.0054-16.2016",
language = "English (US)",
volume = "36",
pages = "7014--7026",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "26",

}

TY - JOUR

T1 - Kif1B interacts with KBP to promote axon elongation by localizing a microtubule regulator to growth cones

AU - Drerup, Catherine M.

AU - Lusk, Sarah

AU - Nechiporuk, Alex

PY - 2016/6/29

Y1 - 2016/6/29

N2 - Delivery of proteins and organelles to the growth cone during axon extension relies on anterograde transport by kinesin motors. Though critical for neural circuit development, the mechanisms of cargo-specific anterograde transport during axon extension are only starting to be explored. Cargos of particular importance for axon outgrowth are microtubule modifiers, such as SCG10 (Stathmin-2). SCG10 is expressed solely during axon extension, localized to growth cones, and essential for axon outgrowth; however, the mechanisms of SCG10 transport and activity were still debated. Using zebrafish mutants and in vivo imaging, we identified the Kif1B motor and its interactor Kif1 binding protein (KBP) as critical for SCG10 transport to axon growth cones and complete axon extension. Axon truncation in kbpst23 mutants can be suppressed by SCG10 overexpression, confirming the direct relationship between decreased SCG10 levels and failed axon outgrowth. Live imaging revealed that the reduced levels of SCG10 in kbpst23 mutant growth cones led to altered microtubule stability, defining the mechanistic basis of axon truncation. Thus, our data reveal a novel role for the Kif1B-KBP complex in the anterograde transport of SCG10, which is necessary for proper microtubule dynamics and subsequent axon extension.

AB - Delivery of proteins and organelles to the growth cone during axon extension relies on anterograde transport by kinesin motors. Though critical for neural circuit development, the mechanisms of cargo-specific anterograde transport during axon extension are only starting to be explored. Cargos of particular importance for axon outgrowth are microtubule modifiers, such as SCG10 (Stathmin-2). SCG10 is expressed solely during axon extension, localized to growth cones, and essential for axon outgrowth; however, the mechanisms of SCG10 transport and activity were still debated. Using zebrafish mutants and in vivo imaging, we identified the Kif1B motor and its interactor Kif1 binding protein (KBP) as critical for SCG10 transport to axon growth cones and complete axon extension. Axon truncation in kbpst23 mutants can be suppressed by SCG10 overexpression, confirming the direct relationship between decreased SCG10 levels and failed axon outgrowth. Live imaging revealed that the reduced levels of SCG10 in kbpst23 mutant growth cones led to altered microtubule stability, defining the mechanistic basis of axon truncation. Thus, our data reveal a novel role for the Kif1B-KBP complex in the anterograde transport of SCG10, which is necessary for proper microtubule dynamics and subsequent axon extension.

KW - Axon extension

KW - KBP

KW - KIF1B

KW - SCG10

KW - Stathmin

UR - http://www.scopus.com/inward/record.url?scp=84976466073&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84976466073&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.0054-16.2016

DO - 10.1523/JNEUROSCI.0054-16.2016

M3 - Article

VL - 36

SP - 7014

EP - 7026

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 26

ER -