Organelle distribution in neurons: Logistics behind polarized transport

Koppers, Max; Farı́as, Ginny G.

doi:10.1016/j.ceb.2021.02.004

Cited by 26 publications

(17 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…, 2014 ; Bentley and Banker, 2016 ; Gumy and Hoogenraad, 2018 ; Radler et al. , 2020 ; Koppers and Farías, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…No movement of more than 30 µm was recorded for endocytosed NgCAM. These results show that endocytosed vesicles rarely move beyond the initial segment, the region of the axon where movement of dendritic vesicles ends (Petersen et al, 2014;Bentley and Banker, 2016;Gumy and Hoogenraad, 2018;Radler et al, 2020;Koppers and Farías, 2021).…”

Section: Ngcam Reaches the Axon By Direct Deliverymentioning

confidence: 98%

See 1 more Smart Citation

NgCAM and VAMP2 reveal that direct delivery and dendritic degradation maintain axonal polarity

Nabb

Bentley

2022

MBoC

View full text Add to dashboard Cite

Neurons are polarized cells of extreme scale and compartmentalization. To fulfill their role in electrochemical signaling, axons must maintain a specific complement of membrane proteins. Despite being subject of considerable attention, the trafficking pathway of axonal membrane proteins is not well understood. Two pathways, direct delivery and transcytosis, have been proposed. Previous studies reached contradictory conclusions about which of these mediates delivery of axonal membrane proteins to their destination, in part because they evaluated long-term distribution changes and not vesicle transport. We developed a novel strategy to selectively label vesicles in different trafficking pathways and determined the trafficking of two canonical axonal membrane proteins, NgCAM and VAMP2. Results from detailed quantitative analyses of transporting vesicles differed substantially from previous studies and found that axonal membrane proteins overwhelmingly undergo direct delivery. Transcytosis plays only a minor role in axonal delivery of these proteins. In addition, we identified a novel pathway by which wayward axonal proteins that reach the dendritic plasma membrane are targeted to lysosomes. These results redefine how axonal proteins achieve their polarized distribution, a crucial requirement for elucidating the underlying molecular mechanisms. [Media: see text] [Media: see text] [Media: see text] [Media: see text]

show abstract

“…, 2014 ; Bentley and Banker, 2016 ; Gumy and Hoogenraad, 2018 ; Radler et al. , 2020 ; Koppers and Farías, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Section: Ngcam Reaches the Axon By Direct Deliverymentioning

confidence: 98%

NgCAM and VAMP2 reveal that direct delivery and dendritic degradation maintain axonal polarity

Nabb

Bentley

2022

MBoC

View full text Add to dashboard Cite

show abstract

“…This raises the intriguing possibility that it represents a neuroprotective mechanism designed to limit viral spread, as proposed previously (Mukherjee et al, 2013 ; Sundaramoorthy et al, 2020 ). Neuronal processes, especially axons, are highly reliant on microtubule-dependent transport for function and survival (De Vos et al, 2008 ; Magiera et al, 2018 ; Guedes-Dias and Holzbaur, 2019 ; Kelliher et al, 2019 ; Koppers and Farías, 2021 ), and several neurotropic viruses including Theiler's virus, herpes simplex virus, poliovirus, rabies virus, and West Nile virus (WNV), transit in axons, likely relying on microtubule-dependent transport to reach their targets (Salinas et al, 2009 and reviewed in Richards et al, 2021 ). Thus, the significant increase in infection and death of neuronal somas in SARM1-depleted cultures (with delayed degeneration of neuronal processes) suggests that ZIKV can be transported in this way too and that SARM1-dependent degeneration of neuronal processes limits its spread to neuronal somas.…”

Section: Discussionmentioning

confidence: 99%

SARM1 Depletion Slows Axon Degeneration in a CNS Model of Neurotropic Viral Infection

Crawford

Antoniou²,

Komarek

et al. 2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Zika virus (ZIKV) is a neurotropic flavivirus recently linked to congenital ZIKV syndrome in children and encephalitis and Guillain-Barré syndrome in adults. Neurotropic viruses often use axons to traffic to neuronal or glial cell somas where they either remain latent or replicate and proceed to infect new cells. Consequently, it has been suggested that axon degeneration could represent an evolutionarily conserved mechanism to limit viral spread. Whilst it is not known if ZIKV transits in axons, we previously reported that ZIKV infection of glial cells in a murine spinal cord-derived cell culture model of the CNS is associated with a profound loss of neuronal cell processes. This, despite that postmitotic neurons are relatively refractory to infection and death. Here, we tested the hypothesis that ZIKV-associated degeneration of neuronal processes is dependent on activation of Sterile alpha and armadillo motif-containing protein 1 (SARM1), an NADase that acts as a central executioner in a conserved axon degeneration pathway. To test this, we infected wild type and Sarm1 homozygous or heterozygous null cell cultures with ZIKV and examined NAD+ levels as well as the survival of neurons and their processes. Unexpectedly, ZIKV infection led to a rapid SARM1-independent reduction in NAD+. Nonetheless, the subsequent profound loss of neuronal cell processes was SARM1-dependent and was preceded by early changes in the appearance of β-tubulin III staining. Together, these data identify a role for SARM1 in the pathogenesis of ZIKV infection, which may reflect SARM1's conserved prodegenerative function, independent of its NADase activity.

show abstract

“…7B), consistent with the idea that at least a subset of growth cone MTs originate in the axon. As well as maintaining axon compartment shape, the uniformity and stability of axonal MT polarity is particularly important for tightly regulated bidirectional transport to and from the growth cone (Koppers and Farias, 2021). In contrast, at least a subset of the MTs in the growth cone are dynamic (Baas and Black, 1990; Edson et al, 1993; Tanaka et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography

Atherton

Stouffer

Francis

et al. 2021

Preprint

View full text Add to dashboard Cite

Neurons navigate long distances and extend axons to form the complex circuitry of the mature brain. This depends on the coordinated response and continuous remodelling of the microtubule and F-actin networks in the axonal growth cone. Growth cone architecture remains poorly understood at nanoscales. We therefore investigated mouse hippocampal neuron growth cones using cryo-electron tomography to directly visualise their three-dimensional subcellular architecture with molecular detail. Our data show the hexagonal arrays of actin bundles that form filopodia penetrate the growth cone interior and terminate in the transition zone. We directly observe the modulation of these and other growth cone actin bundles by alteration of individual F-actin helical structures. Blunt-ended microtubules predominate in the growth cone, frequently contain lumenal particles and carry lattice defects. Investigation of the effect of absence of doublecortin, a neurodevelopmental cytoskeleton regulator, on growth cone cytoskeleton shows no major anomalies in overall growth cone organisation or in F-actin subpopulations. However, our data suggest that microtubules sustain more structural defects, highlighting the importance of microtubule integrity during growth cone migration.

show abstract

Organelle distribution in neurons: Logistics behind polarized transport

Cited by 26 publications

References 55 publications

NgCAM and VAMP2 reveal that direct delivery and dendritic degradation maintain axonal polarity

NgCAM and VAMP2 reveal that direct delivery and dendritic degradation maintain axonal polarity

SARM1 Depletion Slows Axon Degeneration in a CNS Model of Neurotropic Viral Infection

Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography

Contact Info

Product

Resources

About