Beyond the cytoskeleton: The emerging role of organelles and membrane remodeling in the regulation of axon collateral branches

Winkle, Cortney C.; Taylor, Kendra L.; Dent, Erik W.; Gallo, Gianluca; Greif, Karen F.; Gupton, Stephanie L.

doi:10.1002/dneu.22398

Cited by 27 publications

(30 citation statements)

References 144 publications

(193 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Axon branching increases the neuronal plasma membrane surface area, which necessitates insertion of new plasma membrane material ( Winkle, Taylor, Dent, Gallo, Greif, and Gupton, 2016 ). We previously demonstrated that netrin-dependent axon branching and the exuberant axon branching in Trim9 −/− neurons requires SNARE-mediated exocytosis and is associated with increased SNARE-complex assembly and an increased frequency of exocytosis ( Winkle et al.…”

Section: Resultsmentioning

confidence: 99%

TRIM9-dependent ubiquitination of DCC constrains kinase signaling, exocytosis, and axon branching

Plooster

Menon

Winkle

et al. 2017

MBoC

Self Cite

View full text Add to dashboard Cite

In the presence of netrin, tripartite motif protein 9 (TRIM9) promotes deleted in colorectal cancer (DCC) clustering, but TRIM9-dependent ubiquitination of DCC is reduced. Loss of ubiquitination promotes an interaction between DCC and FAK and FAK activation. FAK activation is required for the progression from SNARE assembly to exocytic vesicle fusion, which supplies membrane material for axon branching.

show abstract

Section: Resultsmentioning

confidence: 99%

TRIM9-dependent ubiquitination of DCC constrains kinase signaling, exocytosis, and axon branching

Plooster

Menon

Winkle

et al. 2017

MBoC

Self Cite

View full text Add to dashboard Cite

show abstract

“…The study by Sainath et al (2016) also determined that actin patches associated with mitochondria exhibit more pronounced dynamics than those not associated with mitochondria, in a manner dependent on mitochondrial respiration, further emphasizing the role of axonal mitochondria as determinants of local actin dynamics along axons. For additional treatment of the role of organelles in branch formation the reader is directed to a recent review focusing on this topic (Winkle et al, 2016). …”

Section: Signaling Mechanisms That Regulate Cytoskeletal Dynamics Durmentioning

confidence: 99%

It takes a village to raise a branch: Cellular mechanisms of the initiation of axon collateral branches

Armijo-Weingart

Gallo

2017

Molecular and Cellular Neuroscience

Self Cite

View full text Add to dashboard Cite

The formation of axon collateral branches from the pre-existing shafts of axons is an important aspect of neurodevelopment and the response of the nervous system to injury. This article provides an overview of the role of the cytoskeleton and signaling mechanisms in the formation of axon collateral branches. Both the actin filament and microtubule components of the cytoskeleton are required for the formation of axon branches. Recent work has begun to shed light on how these two elements of the cytoskeleton are integrated by proteins that functionally or physically link the cytoskeleton. While a number of signaling pathways have been determined as having a role in the formation of axon branches, the complexity of the downstream mechanisms and links to specific signaling pathways remain to be fully determined. The regulation of intra-axonal protein synthesis and organelle function are also emerging as components of signal-induced axon branching. Although much has been learned in the last couple of decades about the mechanistic basis of axon branching we can look forward to continue elucidating this complex biological phenomenon with the aim of understanding how multiple signaling pathways, cytoskeletal regulators and organelles are coordinated locally along the axon to give rise to a branch.

show abstract

“…Mitochondria and the endoplasmic reticulum (ER) are functionally and structurally linked organelles that cooperate in calcium signaling and traffic metabolites (Filadi et al, 2017). Both organelles are considered to contribute to axon morphogenesis (Winkle et al, 2016), and the respiration of axonal mitochondria can be controlled by extracellular signals (Verburg and Hollenbeck, 2008;Pacelli et al, 2015;Sainath et al, 2017). However, the regulation of the subcellular distribution of axonal organelles by extracellular signals is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Chondroitin sulfate proteoglycans negatively regulate the positioning of mitochondria and endoplasmic reticulum to distal axons

Sainath

Armijo-Weingart

Ketscheck

et al. 2017

Developmental Neurobiology

Self Cite

View full text Add to dashboard Cite

Chondroitin sulfate proteoglycans (CSPGs) are components of the extracellular matrix that inhibit the extension and regeneration of axons. However, the underlying mechanism of action remains poorly understood. Mitochondria and endoplasmic reticulum (ER) are functionally inter-linked organelles important to axon development and maintenance. We report that CSPGs impair the targeting of mitochondria and ER to the growth cones of chicken embryonic sensory axons. The effect of CSPGs on the targeting of mitochondria is blocked by inhibition of the LAR receptor for CSPGs. The regulation of the targeting of mitochondria and ER to the growth cone by CSPGs is due to attenuation of PI3K signaling, which is known to be downstream of LAR receptor activation. Dynactin is a required component of the dynein motor complex that drives the normally occurring retrograde evacuation of mitochondria from growth cones. CSPGs elevate the levels of p150Glu dynactin found in distal axons, and inhibition of the interaction of dynactin with dynein increased axon lengths on CSPGs. CSPGs also decreased the membrane potential of mitochondria, and pharmacological inhibition of mitochondria respiration at the growth cone independent of manipulation of mitochondria positioning impaired axon extension. Combined inhibition of dynactin and potentiation of mitochondria respiration further increased axon lengths on CSPGs relative to inhibition of dynactin alone. These data reveal that the regulation of the localization of mitochondria and ER to growth cones is a previously unappreciated aspect of the effects of CSPGs on embryonic axons.

show abstract

Beyond the cytoskeleton: The emerging role of organelles and membrane remodeling in the regulation of axon collateral branches

Cited by 27 publications

References 144 publications

TRIM9-dependent ubiquitination of DCC constrains kinase signaling, exocytosis, and axon branching

TRIM9-dependent ubiquitination of DCC constrains kinase signaling, exocytosis, and axon branching

It takes a village to raise a branch: Cellular mechanisms of the initiation of axon collateral branches

Chondroitin sulfate proteoglycans negatively regulate the positioning of mitochondria and endoplasmic reticulum to distal axons

Contact Info

Product

Resources

About