O-GlcNAcylation of tubulin inhibits its polymerization

Ji, Suena; Kang, Jeong Gu; Park, Soo‐Jin; Lee, Joohun; Oh, Young J.; Cho, Jin Won

doi:10.1007/s00726-010-0698-9

Cited by 43 publications

(38 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By inhibiting the phosphorylation of Tyr 272 , O -GlcNAcylation of Thr 271 may regulate microtubule formation and/or interaction with ligands, such as tau, microtubule-associated proteins 1, 2 (MAPs-1, 2), which are also O -GlcNAcylated. Recently it was demonstrated that O -GlcNAcylation of tubulin inhibits its polymerization and negatively regulates microtubule formation [37]. The present results suggest that the reabsorption of certain substances in the proximal tubules by transportation via microtubules may be hampered as polymerization of tubulin is inhibited by its abnormal O -GlcNAcylation.…”

Section: Discussionmentioning

confidence: 55%

Morphological changes in diabetic kidney are associated with increased O-GlcNAcylation of cytoskeletal proteins including α-actinin 4

et al. 2011

View full text Add to dashboard Cite

PurposeThe objective of the present study is to identify proteins that change in the extent of the modification with O-linked N-acetylglucosamine (O-GlcNAcylation) in the kidney from diabetic model Goto-Kakizaki (GK) rats, and to discuss the relation between O-GlcNAcylation and the pathological condition in diabetes.MethodsO-GlcNAcylated proteins were identified by two-dimensional gel electrophoresis, immunoblotting and peptide mass fingerprinting. The level of O-GlcNAcylation of these proteins was examined by immunoprecipitation, immunoblotting and in situ Proximity Ligation Assay (PLA).ResultsO-GlcNAcylated proteins that changed significantly in the degree of O-GlcNAcylation were identified as cytoskeletal proteins (α-actin, α-tubulin, α-actinin 4, myosin) and mitochondrial proteins (ATP synthase β, pyruvate carboxylase). The extent of O-GlcNAcylation of the above proteins increased in the diabetic kidney. Immunofluorescence and in situ PLA studies revealed that the levels of O-GlcNAcylation of actin, α-actinin 4 and myosin were significantly increased in the glomerulus and the proximal tubule of the diabetic kidney. Immunoelectron microscopy revealed that immunolabeling of α-actinin 4 is disturbed and increased in the foot process of podocytes of glomerulus and in the microvilli of proximal tubules.ConclusionThese results suggest that changes in the O-GlcNAcylation of cytoskeletal proteins are closely associated with the morphological changes in the podocyte foot processes in the glomerulus and in microvilli of proximal tubules in the diabetic kidney. This is the first report to show that α-actinin 4 is O-GlcNAcylated. α-Actinin 4 will be a good marker protein to examine the relation between O-GlcNAcylation and diabetic nephropathy.

show abstract

Section: Discussionmentioning

confidence: 55%

Morphological changes in diabetic kidney are associated with increased O-GlcNAcylation of cytoskeletal proteins including α-actinin 4

et al. 2011

View full text Add to dashboard Cite

show abstract

“…37,38 In addition, previous studies have shown that O-GlcNAcylation of tubulin proteins inhibits their polymerization and negatively regulates microtubule formation. 39 These findings suggest that a decrease in O-GlcNAcylation of TUJ1 proteins might be involved in increased microtubule formation and neuronal growth.…”

Section: Resultsmentioning

confidence: 90%

Chemical Modulation of Protein O-GlcNAcylation via OGT Inhibition Promotes Human Neural Cell Differentiation

et al. 2017

View full text Add to dashboard Cite

The enzymes that determine protein O-GlcNAcylation, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), act on key transcriptional and epigenetic regulators, and both are abundantly expressed in the brain. However, little is known about how alterations in O-GlcNAc cycling affect human embryonic stem cell (hESC) neural differentiation. Here, we studied the effects of perturbing O-GlcNAcylation during neural induction of hESCs using the metabolic inhibitor of OGT, peracetylated 5-thio-N-acetylglucosamine (Ac4-5SGlcNAc). Treatment of hESCs with Ac4-5SGlcNAc during induction limited protein O-GlcNAcylation and also caused a dramatic decrease in global levels of UDP-GlcNAc. Concomitantly, a subpopulation of neural progenitor cells (NPCs) acquired an immature neuronal morphology and expressed early neuronal markers such as β-III tubulin (TUJ1) and microtubule associated protein 2 (MAP2), phenotypes that took longer to manifest in the absence of OGT inhibition. These data suggest that chemical inhibition of OGT and perturbation of protein O-GlcNAcylation accelerate the differentiation of hESCs along the neuronal lineage, thus providing further insight into the dynamic molecular mechanisms involved in neuronal development.

show abstract

“…OGT has many substrates, including several such as tubulin, kinesin and dynein with potential impact on mitochondrial dynamics (Ji et al, 2010; Ruan et al, 2012; Trinidad et al, 2012). However, by mapping and mutating four key sites of GlcNAc addition in hMilton1 (hMilton1 Qmut ), we demonstrated that Milton is the key and essential substrate through which OGT inhibits mitochondrial motility.…”

Section: Discussionmentioning

confidence: 99%

Glucose Regulates Mitochondrial Motility via Milton Modification by O-GlcNAc Transferase

Pekkurnaz

Trinidad

Wang

et al. 2014

Cell

229

261

View full text Add to dashboard Cite

SUMMARY Cells allocate substantial resources towards monitoring levels of nutrients that can be used for ATP generation by mitochondria. Among the many specialized cell types, neurons are particularly dependent on mitochondria due to their complex morphology and regional energy needs. Here, we report a molecular mechanism by which nutrient availability in the form of extracellular glucose and the enzyme O-GlcNAc Transferase (OGT), whose activity depends on glucose availability, regulates mitochondrial motility in neurons. Activation of OGT diminishes mitochondrial motility. We establish the mitochondrial motor-adaptor protein Milton as a required substrate for OGT to arrest mitochondrial motility by mapping and mutating the key O-GlcNAcylated serine residues. We find that the GlcNAcylation state of Milton is altered by extracellular glucose and that OGT alters mitochondrial motility in vivo. Our findings suggest that, by dynamically regulating Milton GlcNAcylation, OGT tailors mitochondrial dynamics in neurons based on nutrient availability.

show abstract

O-GlcNAcylation of tubulin inhibits its polymerization

Cited by 43 publications

References 43 publications

Morphological changes in diabetic kidney are associated with increased O-GlcNAcylation of cytoskeletal proteins including α-actinin 4

Morphological changes in diabetic kidney are associated with increased O-GlcNAcylation of cytoskeletal proteins including α-actinin 4

Chemical Modulation of Protein O-GlcNAcylation via OGT Inhibition Promotes Human Neural Cell Differentiation

Glucose Regulates Mitochondrial Motility via Milton Modification by O-GlcNAc Transferase

Contact Info

Product

Resources

About