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
N1 - Publisher Copyright:
© 2016 The Authors.
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
C2 - 27358458
AN - SCOPUS:84976466073
SN - 0270-6474
VL - 36
SP - 7014
EP - 7026
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 26
ER -