Disparate regulatory mechanisms control Fat3 and P75NTR protein transport through a conserved kif5-interaction domain

Haixia Cheng, Jessica Burroughs-Garcia, Jacqueline E. Birkness, Jonathan C. Trinidad, Michael R. Deans

Research output: Contribution to journalArticle

Abstract

Directed transport delivers proteins to specific cellular locations and is one mechanism by which cells establish and maintain polarized cellular architectures. The atypical cadherin Fat3 directs the polarized extension of dendrites in retinal amacrine cells by influencing the distribution of cytoskeletal regulators during retinal development, however the mechanisms regulating the distribution of Fat3 remain unclear. We report a novel Kinesin/Kif5 Interaction domain (Kif5-ID) in Fat3 that facilitates Kif5B binding, and determines the distribution of Fat3 cytosolic domain constructs in neurons and MDCK cells. The Kif5-ID sequence is conserved in the neurotrophin receptor P75NTR, which also binds Kif5B, and Kif5-ID mutations similarly result in P75NTR mislocalization. Despite these similarities, Kif5B-mediated protein transport is differentially regulated by these two cargos. For Fat3, the Kif5-ID is regulated by alternative splicing, and the timecourse of splicing suggests that the distribution of Fat3 may switch between early and later stages of retinal development. In contrast, P75NTR binding to Kif5B is enhanced by tyrosine phosphorylation and thus has the potential to be dynamically regulated on a more rapid time scale.

Original languageEnglish (US)
Article numbere0165519
JournalPLoS One
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

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Nerve Growth Factor Receptors
Amacrine Cells
Kinesin
Phosphorylation
Madin Darby Canine Kidney Cells
protein transport
Conserved Sequence
Alternative Splicing
Protein Transport
Cadherins
Dendrites
Neurons
Tyrosine
Carrier Proteins
Switches
Mutation
kinesin
Proteins
neurotrophins
cadherins

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Cheng, H., Burroughs-Garcia, J., Birkness, J. E., Trinidad, J. C., & Deans, M. R. (2016). Disparate regulatory mechanisms control Fat3 and P75NTR protein transport through a conserved kif5-interaction domain. PLoS One, 11(10), [e0165519]. https://doi.org/10.1371/journal.pone.0165519

Disparate regulatory mechanisms control Fat3 and P75NTR protein transport through a conserved kif5-interaction domain. / Cheng, Haixia; Burroughs-Garcia, Jessica; Birkness, Jacqueline E.; Trinidad, Jonathan C.; Deans, Michael R.

In: PLoS One, Vol. 11, No. 10, e0165519, 01.10.2016.

Research output: Contribution to journalArticle

Cheng, Haixia ; Burroughs-Garcia, Jessica ; Birkness, Jacqueline E. ; Trinidad, Jonathan C. ; Deans, Michael R. / Disparate regulatory mechanisms control Fat3 and P75NTR protein transport through a conserved kif5-interaction domain. In: PLoS One. 2016 ; Vol. 11, No. 10.
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