Paralysis and Early Death in Cysteine String Protein Mutants of
            <i>Drosophila</i>

Zinsmaier, Konrad E.; Eberle, Kai K.; Buchner, Erich; Walter, Niklaus; Benzer, Seymour

doi:10.1126/science.8310297

Cited by 351 publications

(338 citation statements)

References 30 publications

Supporting

Mentioning

322

Contrasting

Order By: Relevance

“…However, we also obtained evidence for a second form of human csp based on cDNA sequence analysis. Precedents exist in Drosophila for csp splice variants [1,9], but it was only very recently that a vertebrate csp splice variant was reported [17]. Interestingly, it appears that the human csp splice variant derives from the same processing mechanism as the bovine form [17].…”

Section: Discussionmentioning

confidence: 99%

Widespread expression of human cysteine string proteins

Coppola¹,

Gundersen²

1996

FEBS Letters

View full text Add to dashboard Cite

We present the nucleotide and deduced amino acid sequences of a human cysteine string protein (csp) and a unique truncated csp variant that derives from the retention of an exonic sequence that introduces a premature, in-frame stop codon. Low stringency Southern analysis is compatible with the presence of a single human csp gene. Northern analysis reveals that human csp mRNA has both a more heterogeneous size distribution and a more widespread tissue distribution than previously reported for other csps. Exemplifying this is the fact that csp immunoreactivity is detected in Triton X-114 extracts of human blood, an observation which may facilitate blood-based diagnostic assays of csp status in man.

show abstract

Section: Discussionmentioning

confidence: 99%

Widespread expression of human cysteine string proteins

Coppola¹,

Gundersen²

1996

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…Another J-protein recently shown to facilitate CHIP-mediated degradation is the cysteine string protein (CSP), which is abundantly expressed in neurons, where it localizes to presynaptic junctions (Schmidt et al, 2009). Deletion of the CSP gene proved to be lethal both in Drosophila and in mice causing a progressive, fatal sensorimotor disorder (Zinsmaier et al, 1994;Fernandez-Chacon et al, 2004). CSP interacts directly with CHIP and facilitates interactions of CHIP with chaperone clients (Schmidt et al, 2009).…”

Section: Figurementioning

confidence: 99%

Chaperone-assisted degradation: multiple paths to destruction

Kettern

Dreiseidler

Tawo³

et al. 2010

Biological Chemistry

153

155

View full text Add to dashboard Cite

Molecular chaperones are well known as facilitators of protein folding and assembly. However, in recent years multiple chaperone-assisted degradation pathways have also emerged, including CAP ( haperone-ssisted roteasomal degradac a p tion), CASA ( haperone-ssisted elective utophagy), and c a s a CMA ( haperone-ediated utophagy). Within these pathc m a ways chaperones facilitate the sorting of non-native proteins to the proteasome and the lysosomal compartment for disposal. Impairment of these pathways contributes to the development of cancer, myopathies, and neurodegenerative diseases. Chaperone-assisted degradation thus represents an essential aspect of cellular proteostasis, and its pharmacological modulation holds the promise to ameliorate some of the most devastating diseases of our time. Here, we discuss recent insights into molecular mechanisms underlying chaperone-assisted degradation in mammalian cells and highlight its biomedical relevance.

show abstract

“…Following one hour incubation with a blocker solution (2-5% bovine serum albumin, 0.2% Tween-20 in PBS, PBT), the preparation was stained overnight at 4 ÂC using primary antisera, followed by one hour washes with PBT and 1-2 hours incubation with secondary antibodies at room temperature, and visualized using a Nikon fluorescence microscope. The following primary antibodies were used: rat anti-Syb (1:300, Wu et al, 1999), mAb anti-CSP (ab49, 1:20, Zinsmaier et al, 1994), rabbit anti-Syt (1:300, Mackler et al, 2002), mAb anti-Futsch (22C10, 1:100, Developmental Studies Hybridoma Bank), mAb anti-Hiw (6H4, 1:3, Wan et al, 2000), rabbit anti-DAP 160 (1:300, Roos and Kelly, 1999), mAb nc82 (1:20; Wagh et al, 2005), a polyclonal antibody to clathrin heavy chain (1:50) and to LAP (1:200, Zhang et al, 1998), a polyclonal antibody to glutamate receptor III (Marrus et al, 2004), a polyclonal antibody to the Drosophila vesicular glutamate transporter (VGluT, 1:500, Daniels et al, 2004), and a polyclonal antibody to HRP (Jan and Jan, 1982). Fluorescence-conjugated secondary antibodies were used 1:100 (Jackson Immunology Labs).…”

Section: Immunocytochemistry and Microscopymentioning

confidence: 99%

The atypical cadherin flamingo regulates synaptogenesis and helps prevent axonal and synaptic degeneration in Drosophila

Bao

Berlanga

Xue

et al. 2007

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

The formation of synaptic connections with target cells and maintenance of axons are highly regulated and crucial for neuronal function. The atypical cadherin and G-protein-coupled receptor Flamingo and its orthologs in amphibians and mammals have been shown to regulate cell polarity, dendritic and axonal growth, and neural tube closure. However, the role of Flamingo in synapse formation and function and in axonal health remains poorly understood. Here we show that fmi mutations cause a significant increase in the number of ectopic synapses on muscles and result in the formation of novel en passant synapses along axons, and unique presynaptic varicosities, including active zones, within axons. fmi mutations also cause defective synaptic responses in a small subset of muscles, an agedependent loss of muscle innervation and a drastic degeneration of axons in 3 rd instar larvae without an apparent loss of neurons. Neuronal expression of Flamingo rescues all of these synaptic and axonal defects and larval lethality. Based on these observations, we propose that Flamingo is required in neurons for synaptic target selection, synaptogenesis, the survival of axons and synapses, and adult viability. These findings shed new light on a possible role for Flamingo in progressive neurodegenerative diseases.

show abstract

Paralysis and Early Death in Cysteine String Protein Mutants of Drosophila

Cited by 351 publications

References 30 publications

Widespread expression of human cysteine string proteins

Widespread expression of human cysteine string proteins

Chaperone-assisted degradation: multiple paths to destruction

The atypical cadherin flamingo regulates synaptogenesis and helps prevent axonal and synaptic degeneration in Drosophila

Contact Info

Product

Resources

About