Sumoylation in axons triggers retrograde transport of the RNA-binding protein La

Niekerk, Erna A. van; Willis, Dianna E.; Chang, Jay; Reumann, Kerstin; Heise, Tilman; Twiss, Jeffery L.

doi:10.1073/pnas.0611562104

Cited by 98 publications

(100 citation statements)

References 34 publications

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“…Furthermore, several SUMO target proteins have important acute effects on neuronal functions. 26 Such proteins include the mRNA-binding protein La, 27 the kainate receptor subunit GluR6 28 and the potassium channel Kv1.5, 29 suggesting a role for SUMO conjugation in ion fluxes and neuronal excitability.…”

Section: Discussionmentioning

confidence: 99%

Transient ischemia induces massive nuclear accumulation of SUMO2/3-conjugated proteins in spinal cord neurons

Wang

Sheng

et al. 2012

Spinal Cord

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Objectives: The objective of this study is to determine whether transient spinal cord ischemia activates small ubiquitin-like modifier (SUMO1-3) conjugation, a post-translational protein modification that protects neurons from ischemia-like conditions. Methods: Mice were subjected to 8-12 min of spinal cord ischemia and 3-24 h of recovery using a newly developed experimental model. To characterize the model, activation of stress response pathways induced after spinal cord ischemia, previously observed in other experimental models, was verified by western blot analysis. Levels and subcellular localization of SUMO-conjugated proteins in spinal cords were evaluated by western blot analysis and immunohistochemistry, respectively. Results: Following transient spinal cord ischemia, stress responses were activated as indicated by increased phosphorylation of eukaryotic initiation factor 2 (eIF2a), extracellular signal-regulated kinases (ERK1/2) and Akt. SUMO1 conjugation was not altered, but a selective rise in levels of SUMO2/3-conjugated proteins occurred, peaking at 6 h reperfusion. The marked activation of SUMO2/ 3 conjugation was a neuronal response to ischemia, as indicated by co-localization with the neuronal marker NeuN, and was associated with nuclear accumulation of SUMO2/3-conjugated proteins. Conclusion: Our study suggests that spinal cord neurons respond to ischemic stress by activation of SUMO2/3 conjugation. Many of the identified SUMO target proteins are transcription factors and other nuclear proteins involved in gene expression and genome stability. It is therefore concluded that the post-ischemic activation of SUMO2/3 conjugation may define the fate of neurons exposed to a transient interruption of blood supply, and that this pathway could be a therapeutic target to increase the resistance of spinal cord neurons to transient ischemia.

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Section: Discussionmentioning

confidence: 99%

Transient ischemia induces massive nuclear accumulation of SUMO2/3-conjugated proteins in spinal cord neurons

Wang

Sheng

et al. 2012

Spinal Cord

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“…Sumoylation of the transcription factor MeCP2 also leads to transcriptional repression, known to play a role in synaptic development (128). Directional transport of proteins in axons has also been shown to be SUMO dependent (129); and sumoylation and phosphorylation have further shown to have synergistic effects (130).…”

Section: Importance Of Proteomics In Identifying Mechanismsmentioning

confidence: 99%

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury

Niekerk

Tuszynski

et al. 2016

Molecular & Cellular Proteomics

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Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. Molecular & Cellular Proteomics

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“…The large population of mRNAs localized to sensory axons (25) indicates that sensory axons have the potential to respond to injury by synthesizing a complex population of proteins. Sumoylation might serve as a mechanism to target axonal proteins for retrograde transport following injury as transport directionality of the RNA-binding protein La in axons is determined by sumoylation (26). Coordination between several injury-signaling pathways may serve as an indicator of the extent and nature of damage.…”

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confidence: 99%

Sunday Driver Interacts with Two Distinct Classes of Axonal Organelles

Abe

Almenar-Queralt

Lillo

et al. 2009

Journal of Biological Chemistry

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The extreme polarized morphology of neurons poses a challenging problem for intracellular trafficking pathways. The distant synaptic terminals must communicate via axonal transport with the cell soma for neuronal survival, function, and repair. Multiple classes of organelles transported along axons may establish and maintain the polarized morphology of neurons, as well as control signaling and neuronal responses to extracellular cues such as neurotrophic or stress factors. We reported previously that the motorbinding protein Sunday Driver (syd), also known as JIP3 or JSAP1, links vesicular axonal transport to injury signaling. To better understand syd function in axonal transport and in the response of neurons to injury, we developed a purification strategy based on anti-syd antibodies conjugated to magnetic beads to identify sydassociated axonal vesicles. Electron microscopy analyses revealed two classes of syd-associated vesicles of distinct morphology. To identify the molecular anatomy of syd vesicles, we determined their protein composition by mass spectrometry. Gene Ontology analyses of each vesicle protein content revealed their unique identity and indicated that one class of syd vesicles belongs to the endocytic pathway, whereas another may belong to an anterogradely transported vesicle pool. To validate these findings, we examined the transport and localization of components of syd vesicles within axons of mouse sciatic nerve. Together, our results lead us to propose that endocytic syd vesicles function in part to carry injury signals back to the cell body, whereas anterograde syd vesicles may play a role in axonal outgrowth and guidance.

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Sumoylation in axons triggers retrograde transport of the RNA-binding protein La

Cited by 98 publications

References 34 publications

Transient ischemia induces massive nuclear accumulation of SUMO2/3-conjugated proteins in spinal cord neurons

Transient ischemia induces massive nuclear accumulation of SUMO2/3-conjugated proteins in spinal cord neurons

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury

Sunday Driver Interacts with Two Distinct Classes of Axonal Organelles

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