1,720,967 research outputs found
alpha TAT1 is the major alpha-tubulin acetyltransferase in mice
No full textPost-translational modification of tubulin serves as a powerful means for rapidly adjusting the functional diversity of microtubules. Acetylation of the Îμ -amino group of K40 in α-tubulin is one such modification that is highly conserved in ciliated organisms. Recently, αTAT1, a Gcn5-related N-acetyltransferase, was identified as an α-tubulin acetyltransferase in Tetrahymena and C. elegans. Here we generate mice with a targeted deletion of Atat1 to determine its function in mammals. Remarkably, we observe a loss of detectable K40 α-tubulin acetylation in these mice across multiple tissues and in cellular structures such as cilia and axons where acetylation is normally enriched. Mice are viable and develop normally, however, the absence of Atat1 impacts upon sperm motility and male mouse fertility, and increases microtubule stability. Thus, αTAT1 has a conserved function as the major α-tubulin acetyltransferase in ciliated organisms and has an important role in regulating subcellular specialization of subsets of microtubules
Tubulin acetyltransferase alpha TAT1 destabilizes microtubules Independently of its acetylation activity
No full textAcetylation ofα-tubulin at lysine 40 (K40) is a well-conserved posttranslational modification that marks long-lived microtubules but has poorly understood functional significance. Recently,αTAT1, a member of the Gcn5-relatedN-acetyltransferase superfamily, has been identified as anF-tubulin acetyltransferase in ciliated organisms. Here, we explored the function ofαTAT1 with the aim of understanding the consequences ofαTAT1-mediated microtubule acetylation.Wedemonstrate thatα-tubulin is the major target of αTAT1 but thatαTAT1 also acetylates itself in a regulatory mechanism that is required for effective modification of tubulin.Wefurther show that in mammalian cells,αTAT1 promotes microtubule destabilization and accelerates microtubule dynamics. Intriguingly, this effect persists in anFTAT1 mutant with no acetyltransferase activity, suggesting that interaction ofαTAT1 with microtubules, rather than acetylation per se, is the critical factor regulating microtubule stability. Our data demonstrate thatαTAT1 has cellular functions that extend beyond its classical enzymatic activity as an α-tubulin acetyltransferase ©2013,American Society for Microbiology
Identification of a novel microtubule acetyltransferase ATAT1
No full textMechanotransduktion ist ein Prozess bei welchem die Zelle mechanische Energie in elektrische oder chemische Signale umwandelt. Genetisches Screening in C. elegans erwies sich als hauptsächliche Quelle für Informationen über Moleküle, die bei Mechanotransduktion eine Rolle spielen. Durch das Screening identifizierte Gene wurden mec genannt, da diese einen mechanosensorischen Phänotyp bewirken. Die Funktion fast aller mec Gene wurde sowohl in C. elegans als auch in Säugetieren beschrieben, allerdings ist die Funktion eines Genes, mec-17, bislang unbekannt. Wir identifizierten ATAT1, ein Säugetierhomolog von mec-17 und konnten nachweisen, dass es sich um eine Mikrotubulus Acetyltransferase handelt. Acetylierung des alpha-Tubulin ist eine hochkonservierte posttranslationale Modifikation, welche langlebige Mikrotubuli markiert, aber bislang kaum geklärte funktionale Bedeutung besitzt. Obwohl bereits Tubulin Deacetylasen bekannt sind, ist ATAT1/mec-17 die erste Mikrotubulus Acetyltransferase, die identifiziert werden konnte. Wir konnten zeigen, dass ATAT1 insbesondere im Zentralnervensystem von Säugetieren exprimiert wird und dass es intrazellulär mit Mikrotubuli und Mikrotubuli-assoziierten Proteinen colokalisiert. Unsere Ergebnisse beweisen, dass die Hauptsubstrate von ATAT1 nicht lösliches Tubulin, sondern polymerisierte und stabile Mikrotubuli sind. Des Weiteren acetyliert ATAT1 alpha-Tubulin an Lysin 40. Interessanterweise, acetyliert sich ATAT1 auch selbst, was einem selbstregulatorischen Mechanismus unterliegt, welcher für die effektive Modifikation von Tubulin notwendig ist. In Säugetierzellen wird ATAT1 mittels „end-binding“ Proteinen (EB- 3) zu den Mikrotubuli rekrutiert, wo es die Dynamiken am Plus-Ende beschleunigt und die Destabilisierung der Mikrotubuli fördert. Bemerkenswerterweise bleibt dieser Effekt in ATAT1 Mutationen bestehen die keine Acetylierungsaktivität mehr aufweisen. Dies legt nahe, dass die Interaktion von ATAT1 mit Mikrotubuli ein wichtiger Faktor für die Stabilitätsregulierung der Mikrotubuli ist und nicht nur in der Acetylierung per se eine Rolle spielt. Des Weiteren konnte ich nachweisen, dass C. elegans‘ mit Mutationen in mec-17 neben der Berührungsinsensitivität auch eine beeinträchtigte neuronale Morphologie und eine zerstörte Mikrotubuli-Ultrastruktur aufweisen. Wichtig ist, dass die meistenPhänotypen,einschließlichder Berührungsinsensitivität, durch Gabe von katalytisch inaktiven mec-17 Mutanten und Wildtyp mec-17 wiederhergestellt werden können. Unsere in vitro und in vivo Beweise legen nahe, dass es sich bei mec-17/ATAT1 um eine wichtige Acetyltransferase von Mikrotubuli handelt, deren Funktion über die enzymatische Aktivität hinaus geht
Genetically Separable Functions of the MEC-17 Tubulin Acetyltransferase Affect Microtubule Organization
No full textSummaryBackgroundMicrotubules (MTs) are formed from the lateral association of 11–16 protofilament chains of tubulin dimers, with most cells containing 13-protofilament (13-p) MTs. How these different MTs are formed is unknown, although the number of protofilaments may depend on the nature of the α- and β-tubulins.ResultsHere we show that the enzymatic activity of the Caenorhabiditis elegans α-tubulin acetyltransferase (α-TAT) MEC-17 allows the production of 15-p MTs in the touch receptor neurons (TRNs) MTs. Without MEC-17, MTs with between 11 and 15 protofilaments are seen. Loss of this enzymatic activity also changes the number and organization of the TRN MTs and affects TRN axonal morphology. In contrast, enzymatically inactive MEC-17 is sufficient for touch sensitivity and proper process outgrowth without correcting the MT defects. Thus, in addition to demonstrating that MEC-17 is required for MT structure and organization, our results suggest that the large number of 15-p MTs, normally found in the TRNs, is not essential for mechanosensation.ConclusionThese experiments reveal a specific role for α-TAT in the formation of MTs and in the production of higher order MTs arrays. In addition, our results indicate that the α-TAT protein has functions that require acetyltransferase activity (such as the determination of protofilament number) and others that do not (presence of internal MT structures)
Inheritance and flexibility of cell polarity : a clue for understanding human brain development and evolution
Full text linkCell polarity is fundamentally important for understanding brain development. Here, we hypothesize that the inheritance and flexibility of cell polarity during neocortex development could be implicated in neocortical evolutionary expansion. Molecular and morphological features of cell polarity may be inherited from one type of progenitor cell to the other and finally transmitted to neurons. Furthermore, key cell types, such as basal progenitors and neurons, exhibit a highly flexible polarity. We suggest that both inheritance and flexibility of cell polarity are implicated in the amplification of basal progenitors and tangential dispersion of neurons, which are key features of the evolutionary expansion of the neocortex.Peer reviewe
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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