BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon
Open accessAbstract
Significance: Lysosomes are found in all neuronal domains, including the soma, axon, and dendrites. How neurons are transported in these domains, however, remains poorly understood. In the present study, we show that a protein ensemble comprising BORC, Arl8, SKIP, and kinesin-1 specifically drives lysosome transport into the axon and not the dendrites. We also show that this mechanism of axonal lysosome transport is essential for maintenance of growth-cone dynamics and turnover of autophagosomes in the distal axon. These findings imply that transport of lysosomes into the axon and the dendrites occurs by different mechanisms, and demonstrate that BORC-regulated lysosome transport is critical for axonal functions.
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The G234A rigor mutant of Kinesin-1 binds to and effectively decorates acetylated microtubules.
“Similar to the active motor, the G234A rigor mutant of Kinesin-1 binds to and effectively decorates acetylated MTs (Tas et al., 2017; Guardia et al., 2016; Farías et al., 2017).”
From A live-cell marker to visualize the dynamics of stable microtubules throughout the cell cycle (2023) · cites this paper as Farías et al., 2017
The Results (Fig. 5F; page not provided) report that a kinesin-1 rigor mutant binds to and decorates microtubule tracks in the initial axon. The paper identifies the mutant as G235A, not G234A, and does not identify those tracks as acetylated microtubules. (LLM, conf=0.88)
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Kinesin superfamily motor proteins and intracellular transport
Hirokawa, N., Noda, Y., Tanaka, Y., & Niwa, S. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2774 · Cited by 1,859 · cited 1× · see citing works
“Specific patterns of organelle distribution in neurons are partly the result of the organelles’ ability to move along different microtubule tracks through coupling to different microtubule motors (17, 18).”
BackgroundRagulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1
Bar-Peled, L., Schweitzer, L. D., Zoncu, R., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.07.032 · Cited by 918 · cited 11× · see citing works
“The axonal LAMP1-GFP colocalized with endogenous LAMTOR4 and Magic Red product, but not the endogenous early endosomal antigen 1 (EEA1) and synaptic vesicle protein synaptophysin-1 (Syp1; Fig.”
BackgroundInfluentialAutophagosomes initiate distally and mature during transport toward the cell soma in primary neurons
Maday, S., Wallace, K. E., & Holzbaur, E. L. F. (2012) · Journal of Cell Biology · doi:10.1083/jcb.201106120 · Cited by 681 · cited 4× · see citing works
“This conclusion is consistent with the notion that fusion of lysosomes with autophagosomes contributes to the dynein-dependent retrograde transport of the resulting autolysosomes, in addition to the degradation of their contents (31, 53).”
BackgroundResultInfluentialTanaka, Y., Kanai, Y., Okada, Y., Nonaka, S., Takeda, S., Harada, A., & Hirokawa, N. (1998) · Cell · doi:10.1016/s0092-8674(00)81459-2 · Cited by 654 · see citing works
The position of lysosomes within the cell determines their luminal pH
Johnson, D. E., Ostrowski, P., Jaumouillé, V., & Grinstein, S. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201507112 · Cited by 590 · see citing works
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Axonal transport: Driving synaptic function
Guedes-Dias, P., & Holzbaur, E. L. F. (2019) · Science · doi:10.1126/science.aaw9997 · Cited by 355 · see citing works
Degradation of engulfed mitochondria is rate-limiting in Optineurin-mediated mitophagy in neurons
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“DOI: https://doi.org/10.7554/eLife.50260 20 of 30 was generated from site-directed mutagenesis, untagged-Parkin (mCherry-Parkin was removed), YFP-NavII-III (Addgene 26056), GFP-Ub (Addgene 11928), TBK1 (Addgene 23851) was recloned into a pSNAPf vector (New England Biolabs), LAMP1-EGFP was subcloned from Addgene 1817 w…”
MethodInfluentialDetyrosinated microtubules spatially constrain lysosomes facilitating lysosome-autophagosome fusion
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A live-cell marker to visualize the dynamics of stable microtubules throughout the cell cycle
Jansen, K. I., Iwanski, M. K., Burute, M., & Kapitein, L. C. (2023) · Journal of Cell Biology · doi:10.1083/jcb.202106105 · Cited by 39 · see citing works
The needs of a synapse—How local organelles serve synaptic proteostasis
Grochowska, K. M., Andres‐Alonso, M., Karpova, A., & Kreutz, M. R. (2022) · The EMBO Journal · doi:10.15252/embj.2021110057 · Cited by 38 · see citing works
- Authors
- Farías, G. G., Guardia, C. M., De Pace, R., Britt, D. J., & Bonifacino, J. S.
- Affiliations
- Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
- National Institutes of Health (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-03-20
- Volume
- 114
- Issue
- 14
- Pages
- E2955-E2964
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5389300
- OpenAlex
- W2600386456
- Cited by
- 228
- References
- 5
- Citations by year
- 2026: 18 · 2025: 18 · 2024: 35 · 2023: 23 · 2022: 32 · 2021: 29 · 2020: 24 · 2019: 22 · 2018: 21 · 2017: 6
- FWCI
- 10.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Intramural Program of NICHD, NIH (ZIA HD001607)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- lysosome transport, axons, polarized transport, SKIP, kinesin-1, axonal growth cones, dendrites, hippocampal neurons
- MeSH terms
- Autophagosomes, Animals, Axons, Biological Transport, Cells, Cultured, Dendrites, Hippocampus, Lysosomes, Neurons, Transcription Factors, Kinesins, ADP-Ribosylation Factors, Multiprotein Complexes, Rats, Rats, Transgenic
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