Tubulin must be acetylated in order to form a complex with membrane Na+,K+-ATPase and to inhibit its enzyme activity

Santander, Verónica S.; Bisig, C. Gastón; Purro, Silvia A.; Casale, César H.; Arce, Carlos A.; Barra, Héctor S.

doi:10.1007/s11010-006-9212-9

Cited by 42 publications

(55 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…and K ? -ATPase activity [165][166][167][168][169]. Expression of an acetylation-resistant a-tubulin mutant significantly inhibits adipogenesis [170], suggesting that adipocyte differentiation is dependent on tubulin acetylation.…”

Section: Tubulin Acetylation In Stress and Other Signaling Pathwaysmentioning

confidence: 99%

Tubulin acetylation: responsible enzymes, biological functions and human diseases

Yang

2015

Cell. Mol. Life Sci.

213

184

View full text Add to dashboard Cite

Microtubules have important functions ranging from maintenance of cell morphology to subcellular transport, cellular signaling, cell migration, and formation of cell polarity. At the organismal level, microtubules are crucial for various biological processes, such as viral entry, inflammation, immunity, learning and memory in mammals. Microtubules are subject to various covalent modifications. One such modification is tubulin acetylation, which is associated with stable microtubules and conserved from protists to humans. In the past three decades, this reversible modification has been studied extensively. In mammals, its level is mainly governed by opposing actions of α-tubulin acetyltransferase 1 (ATAT1) and histone deacetylase 6 (HDAC6). Knockout studies of the mouse enzymes have yielded new insights into biological functions of tubulin acetylation. Abnormal levels of this modification are linked to neurological disorders, cancer, heart diseases and other pathological conditions, thereby yielding important therapeutic implications. This review summarizes related studies and concludes that tubulin acetylation is important for regulating microtubule architecture and maintaining microtubule integrity. Together with detyrosination, glutamylation and other modifications, tubulin acetylation may form a unique 'language' to regulate microtubule structure and function.

show abstract

Section: Tubulin Acetylation In Stress and Other Signaling Pathwaysmentioning

confidence: 99%

Tubulin acetylation: responsible enzymes, biological functions and human diseases

Yang

2015

Cell. Mol. Life Sci.

213

184

View full text Add to dashboard Cite

show abstract

“…In addition to mitochondrial membranes, tubulin has been shown to interact with proteins associated with other membranes (14,15). Tubulin is a heterodimer, composed of similar 50-kDa globular ␣ and ␤ subunits.…”

mentioning

confidence: 99%

Tubulin binding blocks mitochondrial voltage-dependent anion channel and regulates respiration

Rostovtseva

Sheldon²,

Hassanzadeh³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

322

330

View full text Add to dashboard Cite

Regulation of mitochondrial outer membrane (MOM) permeability has dual importance: in normal metabolite and energy exchange between mitochondria and cytoplasm and thus in control of respiration, and in apoptosis by release of apoptogenic factors into the cytosol. However, the mechanism of this regulation, dependent on the voltage-dependent anion channel (VDAC), the major channel of MOM, remains controversial. A long-standing puzzle is that in permeabilized cells, adenine nucleotide translocase (ANT) is less accessible to cytosolic ADP than in isolated mitochondria. We solve this puzzle by finding a missing player in the regulation of MOM permeability: the cytoskeletal protein tubulin. We show that nanomolar concentrations of dimeric tubulin induce voltage-sensitive reversible closure of VDAC reconstituted into planar phospholipid membranes. Tubulin strikingly increases VDAC voltage sensitivity and at physiological salt conditions could induce VDAC closure at <10 mV transmembrane potentials. Experiments with isolated mitochondria confirm these findings. Tubulin added to isolated mitochondria decreases ADP availability to ANT, partially restoring the low MOM permeability (high apparent K m for ADP) found in permeabilized cells. Our findings suggest a previously unknown mechanism of regulation of mitochondrial energetics, governed by VDAC and tubulin at the mitochondriacytosol interface. This tubulin-VDAC interaction requires tubulin anionic C-terminal tail (CTT) peptides. The significance of this interaction may be reflected in the evolutionary conservation of length and anionic charge in CTT throughout eukaryotes, despite wide changes in the exact sequence. Additionally, tubulins that have lost significant length or anionic character are only found in cells that do not have mitochondria.xidative phosphorylation requires transport of metabolites, including cytosolic ADP, ATP, and inorganic phosphate, across both mitochondrial membranes for F 1 F 0 -ATPase to generate ATP in the matrix. Voltage-dependent anion channel (VDAC, also called mitochondrial porin) is the most abundant protein in mitochondrial outer membrane (MOM) and is known to be primarily responsible for ATP/ADP flux across the outer membrane (1, 2). Until recently, VDAC was generally viewed as a part of the pathway for release of cytochrome c and other apoptogenic factors from the mitochondrial intermembrane space into the cytosol at the early stage of apoptosis. The recent genetic studies undermined this view (3) but still left open a lot of questions concerning the role of VDAC in MOM permeabilization in apoptosis (4-6). A conserved property of VDACs in vitro is the ability to adopt a unique fully open state and multiple states with significantly smaller conductance (7). It was demonstrated that the latter, so called ''closed states'' are impermeable to ATP but still permeable to small ions (8), including Ca 2ϩ (9). In isolated mitochondria, respiration is characterized by an apparent K m for exogenous ADP that is Ϸ10-fold lower than in permeabilize...

show abstract

“…In an interesting model, Jackson [101] discussed the possible role of N-terminal acetylation of GTPases, and subsequent association of this enzyme with membrane, a process that further influences membrane trafficking and organelle structure in eukaryotic cells. Cytoskeletal proteins such as cytokeratins [102], tubulin [103][104][105] and myosin [99,106] can also be acetylated, and this PTM can influence their association with the plasma membrane. Casale et al [103] and Santander et al [104] have shown that the brain plasma membrane Na 1 , K 1 -ATP-ase is inhibited by acetylated tubulin.…”

Section: Acetylationmentioning

confidence: 99%

“…Cytoskeletal proteins such as cytokeratins [102], tubulin [103][104][105] and myosin [99,106] can also be acetylated, and this PTM can influence their association with the plasma membrane. Casale et al [103] and Santander et al [104] have shown that the brain plasma membrane Na 1 , K 1 -ATP-ase is inhibited by acetylated tubulin. Moreover, tubulin must be acetylated in order to form a complex with this enzyme [105].…”

Section: Acetylationmentioning

confidence: 99%

Mammalian plasma membrane proteins as potential biomarkers and drug targets

2011

View full text Add to dashboard Cite

Defining the plasma membrane proteome is crucial to understand the role of plasma membrane in fundamental biological processes. Change in membrane proteins is one of the first events that take place under pathological conditions, making plasma membrane proteins a likely source of potential disease biomarkers with prognostic or diagnostic potential. Membrane proteins are also potential targets for monoclonal antibodies and other drugs that block receptors or inhibit enzymes essential to the disease progress. Despite several advanced methods recently developed for the analysis of hydrophobic proteins and proteins with posttranslational modifications, integral membrane proteins are still under-represented in plasma membrane proteome. Recent advances in proteomic investigation of plasma membrane proteins, defining their roles as diagnostic and prognostic disease biomarkers and as target molecules in disease treatment, are presented.

show abstract

Tubulin must be acetylated in order to form a complex with membrane Na+,K+-ATPase and to inhibit its enzyme activity

Cited by 42 publications

References 30 publications

Tubulin acetylation: responsible enzymes, biological functions and human diseases

Tubulin acetylation: responsible enzymes, biological functions and human diseases

Tubulin binding blocks mitochondrial voltage-dependent anion channel and regulates respiration

Mammalian plasma membrane proteins as potential biomarkers and drug targets

Contact Info

Product

Resources

About