The Role of Reticulons in Neurodegenerative Diseases

Chiurchiù, Valerio; Maccarrone, Mauro; Orlacchio, Antonio

doi:10.1007/s12017-013-8271-9

Cited by 68 publications

(71 citation statements)

References 127 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In both yeast and mammalian cells, ER sheets are found juxtaposed to the nucleus, whereas tubular ER is peripherally located away from the nucleus and close to the PM. The high membrane curvature of the ER is stabilized by two reticulon proteins, Rtn1 and Rtn2, and a reticulon-like protein, DP1/Yop1 (Stefano et al, 2014; Chiurchiu et al, 2014; Goyal and Blackstone, 2013; Hu et al, 2011; Friedman and Voeltz, 2011; English et al, 2009). To determine whether an intact cER tubular structure is necessary to establish ER stress-induced functional asymmetry between the cER and pnER, we examined Kar2-sfGFP mobility in cells lacking RTN1 , RTN2 , and YOP1.…”

Section: Resultsmentioning

confidence: 99%

“…Our results with rtn1Δrtn2Δyop1Δ, rtn1Δrtn2Δyop1Δsey1Δ , and rtn1Δrtn2Δyop1Δlnp1Δ cells point to the importance of a balance between reticular and sheet-like structures. RTNs and Yop1 localize preferentially to the cER to maintain the ER tubular structure (Stefano et al, 2014; Chiurchiu et al, 2014; Goyal and Blackstone, 2013; Hu et al, 2011; Friedman and Voeltz, 2011; English et al, 2009). Lnp1 and Sey1 act at three-way junctions in the peripheral ER and at junctions between the reticular and pnER (Chen et al, 2012) and function together to balance the formation of the reticular network.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Reticulons Regulate the ER Inheritance Block during ER Stress

et al. 2016

View full text Add to dashboard Cite

Segregation of functional organelles during the cell cycle is crucial to generate healthy daughter cells. In S. cerevisiae, ER stress causes an ER inheritance block to ensure cells inherit a functional ER. Here, we report that formation of tubular ER in the mother cell, the first step in ER inheritance, depends on functional symmetry between the cortical ER (cER) and perinuclear ER (pnER). ER stress induces functional asymmetry, blocking tubular ER formation and ER inheritance. Using fluorescence recovery after photobleaching, we show that the ER chaperone Kar2/BiP fused to GFP and an ER membrane reporter, Hmg1-GFP, behave differently in the cER and pnER. The functional asymmetry and tubular ER formation depend on Reticulons/Yop1, which maintain ER structure. Lunapark1 deletion in rtn1Δrtn2Δyop1Δ cells restores the pnER/cER functional asymmetry, tubular ER generation and ER inheritance blocks. Thus, Reticulon/Yop1-dependent changes in ER structure are linked to ER inheritance during the yeast cell cycle.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reticulons Regulate the ER Inheritance Block during ER Stress

et al. 2016

View full text Add to dashboard Cite

show abstract

“…These proteins regulate ER structure and functions and contain a uniquely conserved C-terminal domain (reticulon homology domain, RHD). RHD contains two putative transmembrane domains (TM1 and TM2), a loop region and a short Nterminus (reviewed in Chiurchiù et al, 2014). Reticulon 2 interacts with spastin.…”

Section: Spg12mentioning

confidence: 99%

Hereditary spastic paraplegia: Clinical-genetic characteristics and evolving molecular mechanisms

Giudice

Lombardi

Santorelli

et al. 2014

Experimental Neurology

Self Cite

294

278

View full text Add to dashboard Cite

Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurological disorders characterized by pathophysiologic hallmark of length-dependent distal axonal degeneration of the corticospinal tracts. The prominent features of this pathological condition are progressive spasticity and weakness of the lower limbs. To date, 72 spastic gait disease-loci and 55 spastic paraplegia genes (SPGs) have been identified. All modes of inheritance (autosomal dominant, autosomal recessive, and X-linked) have been described. Recently, a late onset spastic gait disorder with maternal trait of inheritance has been reported, as well as mutations in genes not yet classified as spastic gait disease. Several cellular processes are involved in its pathogenesis, such as membrane and axonal transport, endoplasmic reticulum membrane modeling and shaping, mitochondrial function, DNA repair, autophagy, and abnormalities in lipid metabolism and myelination processes. Moreover, recent evidences have been found about the impairment of endosome membrane trafficking in vesicle formation and about the involvement of oxidative stress and mtDNA polymorphisms in the onset of the disease. Interactome networks have been postulated by bioinformatics and biological analyses of spastic paraplegia genes, which would contribute to the development of new therapeutic approaches.

show abstract

“…Differential up-and down-regulation of RTNs have been linked to neurodegenerative diseases (e.g. Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, as well as hereditary spastic paraplegia) (62)(63)(64). RTN1A has been implicated in the onset of several neurodegenerative diseases; however, what role it plays is unknown (62,65).…”

Section: Rtn1a Promotes Er-mitochondrial Contactsmentioning

confidence: 99%

Ascorbate peroxidase proximity labeling coupled with biochemical fractionation identifies promoters of endoplasmic reticulum–mitochondrial contacts

Cho

Adelmant

Lim

et al. 2017

Journal of Biological Chemistry

100

View full text Add to dashboard Cite

Edited by John M. DenuTo maintain cellular homeostasis, subcellular organelles communicate with each other and form physical and functional networks through membrane contact sites coupled by protein tethers. In particular, endoplasmic reticulum (ER)-mitochondrial contacts (EMC) regulate diverse cellular activities such as metabolite exchange (Ca 2؉ and lipids), intracellular signaling, apoptosis, and autophagy. The significance of EMCs has been highlighted by reports indicating that EMC dysregulation is linked to neurodegenerative diseases. Therefore, obtaining a better understanding of the physical and functional components of EMCs should provide new insights into the pathogenesis of several neurodegenerative diseases. Here, we applied engineered ascorbate peroxidase (APEX) to map the proteome at EMCs in live HEK293 cells. APEX was targeted to the outer mitochondrial membrane, and proximity-labeled proteins were analyzed by stable isotope labeling with amino acids in culture (SILAC)-LC/MS-MS. We further refined the specificity of the proteins identified by combining biochemical subcellular fractionation to the protein isolation method. We identified 405 proteins with a 2.0-fold cutoff ratio (log base 2) in SILAC quantification from replicate experiments. We performed validation screening with a Split-Rluc8 complementation assay that identified reticulon 1A (RTN1A), an ER-shaping protein localized to EMCs as an EMC promoter. Proximity mapping augmented with biochemical fractionation and additional validation methods reported here could be useful to discover other components of EMCs, identify mitochondrial contacts with other organelles, and further unravel their communication.

show abstract

The Role of Reticulons in Neurodegenerative Diseases

Cited by 68 publications

References 127 publications

Reticulons Regulate the ER Inheritance Block during ER Stress

Reticulons Regulate the ER Inheritance Block during ER Stress

Hereditary spastic paraplegia: Clinical-genetic characteristics and evolving molecular mechanisms

Ascorbate peroxidase proximity labeling coupled with biochemical fractionation identifies promoters of endoplasmic reticulum–mitochondrial contacts

Contact Info

Product

Resources

About