Multiple layers of spatial regulation coordinate axonal cargo transport

Selective axonal transport through branch junctions is directed by growth cone signaling and mediated by KIF1/kinesin-3 motors

“…Moreover, shRNA knockdown demonstrates the requirement of KIF1 but not KIF5 for signal-dependent transport selectivity of LAMP1 vesicles ( Figure 4 ). In line with the role of KIF1 in sorting transport at the AIS ( Gumy et al, 2017 ; Leterrier and Dargent, 2014 ; Zahavi and Hoogenraad, 2021 ), our results further suggest that some motors (e.g., KIF5) drive forward movement, while other motors (e.g., KIF1) steer transport along microtubule tracks. Such regulation could be achieved at several possible sites, including motor-vesicle coupling ( Hummel and Hoogenraad, 2021 ), motor activity ( Atherton et al, 2020 ), post-translational modifications of microtubules ( Guedes-Dias et al, 2019 ), and various microtubule-associated proteins ( Monroy et al, 2018 ; Tymanskyj et al, 2018 ).…”

“…In complex mammalian neurons, not only is the long distance a daunting task for transport, but the elaborate branches also pose a navigational challenge for targeted cargo delivery. Although recent studies have begun to elucidate the mechanisms regulating transport in different regions of a neuron ( Britt et al, 2016 ; Guedes-Dias et al, 2019 ; Huang and Banker, 2012 ; Lipka et al, 2016 ; Nakata and Hirokawa, 2003 ; Nirschl et al, 2016 ; Zahavi and Hoogenraad, 2021 ), our understanding of how cargos navigate the branched architecture remains under-studied.…”

Metabolic and Cellular Compartments of Acetyl-CoA in the Healthy and Diseased Brain

“…In the adult brain, axonal transport is indispensable for survival, integrity and proper neuronal function. Microtubules are involved in the bidirectional transport of proteins and trophic factors, signalling peptides and organelles, including mitochondria, between neuronal perikaryon and nerve terminals [ 64 , 66 ] ( Figure 3 ). The biogenesis of mitochondria takes place in neuronal perikaryons, as the majority of mitochondrial proteins are encoded by nuclear DNA.…”

Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration

“…The axonal anterograde mitochondrial transport machinery includes adaptor protein trafficking kinesin protein 1 (TRAK1), which connects mitochondria through the mitochondria outer membrane molecule 4 Miro1 to the microtubule motor proteins kinesin-1 family (KIF5A-C) 13,14,28,29 . Interestingly, OPTN is also known to coordinate intracellular vesicular trafficking through multiple binding partners [9][10][11] , but, it has not been linked to mitochondria axonal transport.…”

“…Proper axonal delivery of mitochondria is crucial for maintaining axon integrity; reduced anterograde movement of mitochondria into axons has been found in mouse models of Alzheimer’s disease (AD) 15–17 , Huntington’s disease (HD) 18, 19 , ALS 20–22 and glaucoma 23–27 . The axonal anterograde mitochondrial transport machinery includes adaptor protein trafficking kinesin protein 1 (TRAK1), which connects mitochondria through the mitochondria outer membrane molecule Miro1 to the microtubule motor proteins kinesin-1 family (KIF5A-C) 13, 14, 28, 29 . Interestingly, OPTN is also known to coordinate intracellular vesicular trafficking through multiple binding partners 9–11 , but, it has not been linked to mitochondria axonal transport.…”