Proteomic cell surface phenotyping of differentiating acute myeloid leukemia cells

Hofmann, Andreas; Gerrits, Bertran; Schmidt, Alexander; Bock, Thomas; Bausch-Fluck, Damaris; Aebersold, Rudolf; Wollscheid, Bernd

doi:10.1182/blood-2010-02-271270

Cited by 79 publications

(77 citation statements)

References 47 publications

(52 reference statements)

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“…In-depth studies of membrane proteins have proven to be difficult because of their low abundance and hydrophobicity 1,4 . However, recent advances in proteomic technologies make it possible to investigate proteins in this cell compartment, including previously unannotated membrane proteins, to an impressive depth [4][5][6][7][8][9] . In this study, we applied colloidal silica-bead coating 10 to enrich for conserved cell-surface-associated proteins in mouse neonatal and human fetal ventricular cardiomyocytes.…”

Section: Resultsmentioning

confidence: 99%

Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function

et al. 2015

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Membrane proteins are crucial to heart function and development. Here we combine cationic silica-bead coating with shotgun proteomics to enrich for and identify plasma membrane-associated proteins from primary mouse neonatal and human fetal ventricular cardiomyocytes. We identify Tmem65 as a cardiac-enriched, intercalated disc protein that increases during development in both mouse and human hearts. Functional analysis of Tmem65 both in vitro using lentiviral shRNA-mediated knockdown in mouse cardiomyocytes and in vivo using morpholino-based knockdown in zebrafish show marked alterations in gap junction function and cardiac morphology. Molecular analyses suggest that Tmem65 interaction with connexin 43 (Cx43) is required for correct localization of Cx43 to the intercalated disc, since Tmem65 deletion results in marked internalization of Cx43, a shorter half-life through increased degradation, and loss of Cx43 function. Our data demonstrate that the membrane protein Tmem65 is an intercalated disc protein that interacts with and functionally regulates ventricular Cx43.

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Section: Resultsmentioning

confidence: 99%

Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function

et al. 2015

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“…Pannexins are known to perform functions in intracellular Ca 2þ signalling, acting as Ca 2þ -leak channels in the ER. LRRC8 proteins also lack a signal peptide and are subjected to glycosylation, at least in the case of LRRC8A and D, the two most widely expressed paralogues [30]. Moreover, LRRC8A and D have been found at the surface of the cell [30] and LRRC8C at the ER [3].…”

Section: Subcellular Localisation Of Lrrc8 Proteins Resembles That Ofmentioning

confidence: 99%

“…3). Furthermore, a characterisation of the cell surface proteome [30] identified peptides located at what our model would propose as the first extracellular loop of LRRC8A and D.…”

Section: Lrrc8 Proteins May Form Hexameric Channelsmentioning

confidence: 99%

“…There are two large and sequencevariable insertions in LRRC8 proteins in the TM1-2 and TM2-3 loops. High throughput proteomic experiments show that these insertions are the target of different post-translational modifications: (i) the insertion between the first and second TM helices is subjected to Nlinked glycosylation, at least in LRRC8A and D [30]; (ii) the insertion between the second and third TM helices is particularly rich in serine and threonine residues, most of which can be phosphorylated [31][32][33][34][35][36] and (iii), several lysine residues in the latter insertion are acetylated [37] or ubiquitinated [38] (Fig. 2).…”

Section: Lrrc8 Proteins May Form Hexameric Channelsmentioning

confidence: 99%

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LRRC8 proteins share a common ancestor with pannexins, and may form hexameric channels involved in cell‐cell communication

2012

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Leucine-rich repeat-containing 8 (LRRC8) proteins are composed of four transmembrane helices and 17 leucine-rich repeats (LRR). Although LRRC8 proteins have been associated with important processes, like maturation of B cells or adipocyte differentiation, their biology and molecular function are largely unknown. We found that LRRC8 proteins originated from the combination of a pannexin and an LRR domain (most likely related to the SHOC2, LAP, RSU1 and LRRIQ4 protein families) before the diversification of chordates. We propose that, like pannexins, LRRC8 proteins form hexameric channels, which participate in cell-cell communication processes. According to the inferred topological model, and contrary to what was previously assumed, the six LRR domains are located in the cytoplasm, and could participate in the organisation of signalling cascades. By compiling available proteomics and gene expression data, and on the basis of the LRRC8 proposed hexameric channel structure, we present clues to the function of this family.

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“…С помощью протеомного метода Hofmann с соавт. исследовали поверхностные белки опухолевых клеток линий HL60 и NB4, индуцированных ATRA [41]. В результате масс-спектрометрического анализа обогащенных мембранных фракций авторы идентифицировали 500 мембранных белков, из которых 137 оказались аннотированными в базах данных CD маркерами.…”

Section: дифференциальное профилирование для исследования поверхностнunclassified

Transcriptomics and proteomics in studies of induced differentiation of leukemia cells

Novikova

Zgoda

2015

BIOMED KHIM

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Proteomic cell surface phenotyping of differentiating acute myeloid leukemia cells

Cited by 79 publications

References 47 publications

Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function

Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function

LRRC8 proteins share a common ancestor with pannexins, and may form hexameric channels involved in cell‐cell communication

Transcriptomics and proteomics in studies of induced differentiation of leukemia cells

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