Proteomic analysis of the palmitoyl protein thioesterase 1 interactome in SH-SY5Y human neuroblastoma cells

Scifo, Enzo; Szwajda, Agnieszka; Soliymani, Rabah; Pezzini, Francesco; Bianchi, Marzia; Dapkunas, Arvydas; Dębski, Janusz; Uusi-Rauva, Kristiina; Dadlez, Michał; Gingras, Anne‐Claude; Tyynelä, Jaana; Simonati, Alessandro; Jalanko, Anu; Baumann, Marc; Łałowski, Maciej

doi:10.1016/j.jprot.2015.03.038

Cited by 53 publications

(72 citation statements)

References 92 publications

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“…This in turn would lead to the transcription of PPT1, through the transcription factor TFEB [27], in an effort to depalmitoylate mutant CSP and degrade it. Over time, CLN4 mutant CSP leads to accumulation of PPT1 and its aggregation, thus preserving the increase of PPT1 and not of other lysosomal proteins, with the exception of saposins and potential PPT1 binding partner Cathepsin D [8, 29]. This should result subsequently in altered PPT1 activity in different subcompartments (Fig.…”

Section: Discussionmentioning

confidence: 99%

Neuronal ceroid lipofuscinosis with DNAJC5/CSPα mutation has PPT1 pathology and exhibit aberrant protein palmitoylation

et al. 2015

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Neuronal Ceroid Lipofuscinoses (NCL) are a group of inherited neurodegenerative disorders with lysosomal pathology (CLN1-14). Recently, mutations in the DNAJC5/CLN4 gene, which encodes the presynaptic co-chaperone CSP were shown to cause autosomal-dominant NCL. Although 14 NCL genes have been identified, it is unknown if they act in common disease pathways. Here we show that two disease-associated proteins, CSPα and the depalmitoylating enzyme palmitoyl-protein thioesterase 1 (PPT1/CLN1) are biochemically linked. We find that in DNAJC5/CLN4 patient brains, PPT1 is massively increased and mis-localized. Surprisingly, the specific enzymatic activity of PPT1 is dramatically reduced. Notably, we demonstrate that CSP is depalmitoylated by PPT1 and hence its substrate. To determine the consequences of PPT1 accumulation, we compared the palmitomes from control and DNAJC5/CLN4 patient brains by quantitative proteomics. We discovered global changes in protein palmitoylation, mainly involving lysosomal and synaptic proteins. Our findings establish a functional link between two forms of NCL and serve as a springboard for investigations of NCL disease pathways.

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Section: Discussionmentioning

confidence: 99%

Neuronal ceroid lipofuscinosis with DNAJC5/CSPα mutation has PPT1 pathology and exhibit aberrant protein palmitoylation

et al. 2015

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“…Ten micrograms of protein from control and PGC‐1α‐tg mice brains was digested using a modified FASP protocol (Scifo et al ., ). In brief, lysate buffer was exchanged by washing it several times with 8 m urea and 0.1 m Tris, pH 8 (urea buffer; UB).…”

Section: Methodsmentioning

confidence: 97%

Peroxisome proliferator‐activated receptor‐γ coactivator‐1α mediates neuroprotection against excitotoxic brain injury in transgenic mice: role of mitochondria and X‐linked inhibitor of apoptosis protein

Mäkelä

Mudò

Pham

et al. 2016

Eur J of Neuroscience

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Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcriptional coactivator involved in the regulation of mitochondrial biogenesis and cell defense. The functions of PGC-1α in physiology of brain mitochondria are, however, not fully understood. To address this we have studied wild-type and transgenic mice with a two-fold overexpression of PGC-1α in brain neurons. Data showed that the relative number and basal respiration of brain mitochondria were increased in PGC-1α transgenic mice compared with wild-type mitochondria. These changes occurred concomitantly with altered levels of proteins involved in oxidative phosphorylation (OXPHOS) as studied by proteomic analyses and immunoblottings. Cultured hippocampal neurons from PGC-1α transgenic mice were more resistant to cell degeneration induced by the glutamate receptor agonist kainic acid. In vivo kainic acid induced excitotoxic cell death in the hippocampus at 48 h in wild-type mice but significantly less so in PGC-1α transgenic mice. However, at later time points cell degeneration was also evident in the transgenic mouse hippocampus, indicating that PGC-1α overexpression can induce a delay in cell death. Immunoblotting showed that X-linked inhibitor of apoptosis protein (XIAP) was increased in PGC-1α transgenic hippocampus with no significant changes in Bcl-2 or Bcl-X. Collectively, these results show that PGC-1α overexpression contributes to enhanced neuronal viability by stimulating mitochondria number and respiration and increasing levels of OXPHOS proteins and the anti-apoptotic protein XIAP.

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“…A more mature neuronal phenotype can be reached using growth medium supplemented with specific chemical factors, such as recombinant human brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), dibutyryl-cyclic AMP (db-cAMP), phorbol esters and others (Agholme et al 2010;Dwane et al 2013;Encinas et al 2000;Gimenez-Cassina et al 2006;Jamsa et al 2004;Kou et al 2008;Kume et al 2008;Sarkanen et al 2007). Thereafter, SH-SY5Y cells have been largely utilized to investigate the disease mechanisms associated with various neurodegenerative disorders (Agholme et al 2014;Ferreira et al 2013;Hadzhieva et al 2013;Jamsa et al 2004;Ke et al 2012;Krishna et al 2014;Lim et al 2015;Lopes et al 2010Lopes et al , 2012Palomo et al 2011;Scifo et al 2013Scifo et al , 2015.…”

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confidence: 99%

Transcriptomic Profiling Discloses Molecular and Cellular Events Related to Neuronal Differentiation in SH-SY5Y Neuroblastoma Cells

et al. 2016

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Human SH-SY5Y neuroblastoma cells are widely utilized in in vitro studies to dissect out pathogenetic mechanisms of neurodegenerative disorders. These cells are considered as neuronal precursors and differentiate into more mature neuronal phenotypes under selected growth conditions. In this study, in order to decipher the pathways and cellular processes underlying neuroblastoma cell differentiation in vitro, we performed systematic transcriptomic (RNA-seq) and bioinformatic analysis of SH-SY5Y cells differentiated according to a two-step paradigm: retinoic acid treatment followed by enriched neurobasal medium. Categorization of 1989 differentially expressed genes (DEGs) identified in differentiated cells functionally linked them to changes in cell morphology including remodelling of plasma membrane and cytoskeleton, and neuritogenesis. Seventy-three DEGs were assigned to axonal guidance signalling pathway, and the expression of selected gene products such as neurotrophin receptors, the functionally related SLITRK6, and semaphorins, was validated by immunoblotting. Along with these findings, the differentiated cells exhibited an ability to elongate longer axonal process as assessed by the neuronal cytoskeletal markers biochemical characterization and morphometric evaluation. Recognition of molecular events occurring in differentiated SH-SY5Y cells is critical to accurately interpret the cellular responses to specific stimuli in studies on disease pathogenesis.

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Proteomic analysis of the palmitoyl protein thioesterase 1 interactome in SH-SY5Y human neuroblastoma cells

Cited by 53 publications

References 92 publications

Neuronal ceroid lipofuscinosis with DNAJC5/CSPα mutation has PPT1 pathology and exhibit aberrant protein palmitoylation

Neuronal ceroid lipofuscinosis with DNAJC5/CSPα mutation has PPT1 pathology and exhibit aberrant protein palmitoylation

Peroxisome proliferator‐activated receptor‐γ coactivator‐1α mediates neuroprotection against excitotoxic brain injury in transgenic mice: role of mitochondria and X‐linked inhibitor of apoptosis protein

Transcriptomic Profiling Discloses Molecular and Cellular Events Related to Neuronal Differentiation in SH-SY5Y Neuroblastoma Cells

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