Smart Motors and Cargo Steering Drive Kinesin-mediated Selective Transport

Overview

Journal Mol Cell Neurosci

Specialties Cell Biology
Molecular Biology
Neurology

Date 2020 Jan 24

PMID 31972342

Citations 15

Authors

Alec T Nabb

Madeline Frank

Marvin Bentley

Affiliations

Soon will be listed here.

Abstract

Neurons are polarized cells, with dendrites and axons that require different complements of membrane proteins to fulfill their specialized functions. Membrane proteins are synthesized in the somatodendritic domain and delivered to their target membranes via long-range vesicle transport. Most anterograde vesicle transport is mediated by kinesin motors, but it is unclear how kinesins are targeted to axons or dendrites. Two main models have been proposed to explain kinesin selectivity. In the smart motor model, kinesin selectivity is conferred by a preference of the kinesin motor domain for specific subsets of microtubules. In the cargo steering model, kinesin selectivity is modulated by the vesicular cargo to which the motor is bound. We evaluate the evidence for both models and conclude that while the smart motor model may explain axonal selectivity, cargo steering is required for dendritic selectivity. Future work will determine the relative contributions of these models to polarized transport in living neurons.

Citing Articles

The heterotrimeric kinesin-2 family member KIF3A directly binds to disabled-1 (Dab1).

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Kinesin Regulation in the Proximal Axon is Essential for Dendrite-selective Transport.

Mendoza C, Plowinske C, Montgomery A, Quinones G, Banker G, Bentley M Mol Biol Cell. 2024; 35(6):ar81.

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Polarized transport requires AP-1-mediated recruitment of KIF13A and KIF13B at the trans-Golgi.

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Disruption of axonal transport in neurodegeneration.

Berth S, Lloyd T J Clin Invest. 2023; 133(11).

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References

Gumy L, Katrukha E, Grigoriev I, Jaarsma D, Kapitein L, Akhmanova A . MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- versus KIF5-Dependent Cargo Transport in Sensory Neurons. Neuron. 2017; 94(2):347-362.e7. DOI: 10.1016/j.neuron.2017.03.046. View

Leterrier C, Vacher H, Fache M, Angles dOrtoli S, Castets F, Autillo-Touati A . End-binding proteins EB3 and EB1 link microtubules to ankyrin G in the axon initial segment. Proc Natl Acad Sci U S A. 2011; 108(21):8826-31. PMC: 3102358. DOI: 10.1073/pnas.1018671108. View

Hammond J, Huang C, Kaech S, Jacobson C, Banker G, Verhey K . Posttranslational modifications of tubulin and the polarized transport of kinesin-1 in neurons. Mol Biol Cell. 2009; 21(4):572-83. PMC: 2820422. DOI: 10.1091/mbc.e09-01-0044. View

Karasmanis E, Phan C, Angelis D, Kesisova I, Hoogenraad C, McKenney R . Polarity of Neuronal Membrane Traffic Requires Sorting of Kinesin Motor Cargo during Entry into Dendrites by a Microtubule-Associated Septin. Dev Cell. 2018; 46(2):204-218.e7. PMC: 6396981. DOI: 10.1016/j.devcel.2018.06.013. View

Hirokawa N, Noda Y, Tanaka Y, Niwa S . Kinesin superfamily motor proteins and intracellular transport. Nat Rev Mol Cell Biol. 2009; 10(10):682-96. DOI: 10.1038/nrm2774. View

Okada Y, Yamazaki H, Hirokawa N . The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors. Cell. 1995; 81(5):769-80. DOI: 10.1016/0092-8674(95)90538-3. View

Sampo B, Kaech S, Kunz S, Banker G . Two distinct mechanisms target membrane proteins to the axonal surface. Neuron. 2003; 37(4):611-24. DOI: 10.1016/s0896-6273(03)00058-8. View

Wang H, Kunkel D, Schwartzkroin P, Tempel B . Localization of Kv1.1 and Kv1.2, two K channel proteins, to synaptic terminals, somata, and dendrites in the mouse brain. J Neurosci. 1994; 14(8):4588-99. PMC: 6577177. View

Verhey K, Lizotte D, Abramson T, Barenboim L, Schnapp B, Rapoport T . Light chain-dependent regulation of Kinesin's interaction with microtubules. J Cell Biol. 1998; 143(4):1053-66. PMC: 2132950. DOI: 10.1083/jcb.143.4.1053. View

10.

Stepanova T, Slemmer J, Hoogenraad C, Lansbergen G, Dortland B, De Zeeuw C . Visualization of microtubule growth in cultured neurons via the use of EB3-GFP (end-binding protein 3-green fluorescent protein). J Neurosci. 2003; 23(7):2655-64. PMC: 6742099. View

11.

Jensen C, Watanabe S, Rasmussen H, Schmitt N, Olesen S, Frost N . Specific sorting and post-Golgi trafficking of dendritic potassium channels in living neurons. J Biol Chem. 2014; 289(15):10566-10581. PMC: 4036177. DOI: 10.1074/jbc.M113.534495. View

12.

Tymanskyj S, Yang B, Verhey K, Ma L . MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport. Elife. 2018; 7. PMC: 6133550. DOI: 10.7554/eLife.36374. View

13.

Setou M, Tanaka Y, Kanai Y, Takei Y, Kawagishi M, Hirokawa N . Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites. Nature. 2002; 417(6884):83-7. DOI: 10.1038/nature743. View

14.

Baas P, Black M, Banker G . Changes in microtubule polarity orientation during the development of hippocampal neurons in culture. J Cell Biol. 1989; 109(6 Pt 1):3085-94. PMC: 2115969. DOI: 10.1083/jcb.109.6.3085. View

15.

Fu M, Holzbaur E . Integrated regulation of motor-driven organelle transport by scaffolding proteins. Trends Cell Biol. 2014; 24(10):564-74. PMC: 4177981. DOI: 10.1016/j.tcb.2014.05.002. View

16.

Lipka J, Kapitein L, Jaworski J, Hoogenraad C . Microtubule-binding protein doublecortin-like kinase 1 (DCLK1) guides kinesin-3-mediated cargo transport to dendrites. EMBO J. 2016; 35(3):302-18. PMC: 4741305. DOI: 10.15252/embj.201592929. View

17.

Verhey K, Meyer D, Deehan R, Blenis J, Schnapp B, Rapoport T . Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J Cell Biol. 2001; 152(5):959-70. PMC: 2198804. DOI: 10.1083/jcb.152.5.959. View

18.

Silverman M, Kaech S, Ramser E, Lu X, Lasarev M, Nagalla S . Expression of kinesin superfamily genes in cultured hippocampal neurons. Cytoskeleton (Hoboken). 2010; 67(12):784-95. PMC: 2996887. DOI: 10.1002/cm.20487. View

19.

Coy D, Wagenbach M, Howard J . Kinesin takes one 8-nm step for each ATP that it hydrolyzes. J Biol Chem. 1999; 274(6):3667-71. DOI: 10.1074/jbc.274.6.3667. View

20.

Sheng M, Tsaur M, Jan Y, Jan L . Subcellular segregation of two A-type K+ channel proteins in rat central neurons. Neuron. 1992; 9(2):271-84. DOI: 10.1016/0896-6273(92)90166-b. View