Stabilization of neurites in cerebellar granule cells by transglutaminase activity: identification of midkine and galectin-3 as substrates

Mahoney, Sally-Ann; Wilkinson, Marc G.; Smith, Stuart; Haynes, Laurence W.

doi:10.1016/s0306-4522(00)00324-9

Cited by 43 publications

(28 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The aim of this study was to gain insight into the mechanism by which tTG contributes to neuronal differentiation processes (19,20). The results presented in this study clearly demonstrate that tTG greatly facilitates adenylyl cyclase activation, resulting in enhanced cAMP production and subsequent CREB phosphorylation and activation.…”

Section: Discussionmentioning

confidence: 77%

“…In the nervous system, tTG has been postulated to play a role in many different processes such as synaptic plasticity (14,15), release of neurotransmitters (16), long-term potentiation (17), axonal regeneration (9), and neuronal death and/or survival (18). Tissue TG also clearly plays a key role in neuronal differentiation (19,20). Indeed, tTG is both necessary and sufficient for the neuronal differentiation of human neuroblastoma SH-SY5Y cells (20).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Tissue Transglutaminase Directly Regulates Adenylyl Cyclase Resulting in Enhanced cAMP-response Element-binding Protein (CREB) Activation

Tucholski¹,

Johnson

2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Tissue transglutaminase (tTG) is present in the human nervous system and is predominantly localized to neurons. Treatment of human neuroblastoma SH-SY5Y cells with retinoic acid results in increased tTG expression, which is both necessary and sufficient for differentiation. The goal of the present study was to determine whether tTG modulates the activation of the cyclic AMP-response element (CRE)-binding protein, CREB, an event that likely plays a central role in the differentiation of SH-SY5Y cells. SH-SY5Y cells stably transfected with active wild type tTG, tTG without transamidating activity (C277S), an antisense tTG construct that depleted the endogenous levels of tTG, or vector only were used for the study. Treatment with forskolin, an adenylyl cyclase activator, increased that activation-associated phosphorylation of CREB, which was prolonged by tTG overexpression. CRE-reporter gene activity was also significantly elevated in the tTG cells compared with the other cells. The enhancement of CREB phosphorylation/activation in the tTG cells is likely due to the fact that tTG significantly potentiates cAMP production, and our findings indicate that tTG enhances adenylyl cyclase activity by modulating the conformation state of adenylyl cyclase. This is the first study to provide evidence of the mechanism by which tTG may contribute to neuronal differentiation.

show abstract

Section: Discussionmentioning

confidence: 77%

mentioning

confidence: 99%

Tissue Transglutaminase Directly Regulates Adenylyl Cyclase Resulting in Enhanced cAMP-response Element-binding Protein (CREB) Activation

Tucholski¹,

Johnson

2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Of note, Gal-3 is expressed mainly by glial cells (Pesheva et al, 1998;Reichert et al, 1994;Walther et al, 2000) but also by subsets of rat sensory and mouse dorsal root ganglia (DRG) neurons Regan et al, Phosphorylation of adhesion-and growth-regulatory human galectin-3 leads to the induction of axonal branching by local membrane L1 and ERM redistribution 1986). It promotes neural cell adhesion and neurite growth of DRG neurons (Pesheva et al, 1998) and, when covalently cross-linked by transglutaminase activity, it can stabilize the neurites of cerebellar granule cells (Mahoney et al, 2000). In this context, it is attractive to suggest that phosphorylation can act as a molecular switch, for instance, by masking an important site on Gal-3 or creating a new site, thereby modulating the activity profile of Gal-3.…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of adhesion- and growth-regulatory human galectin-3 leads to the induction of axonal branching by local membrane L1 and ERM redistribution

Díez-Revuelta

Velasco

André

et al. 2010

Journal of Cell Science

View full text Add to dashboard Cite

SummarySerine phosphorylation of the -galactoside-binding protein galectin-3 (Gal-3) impacts nuclear localization but has unknown consequences for extracellular activities. Herein, we reveal that the phosphorylated form of galectin-3 (pGal-3), adsorbed to substratum surfaces or to heparan sulphate proteoglycans, is instrumental in promoting axon branching in cultured hippocampal neurons by local actin destabilization. pGal-3 interacts with neural cell adhesion molecule L1, and enhances L1 association with Thy-1-rich membrane microdomains. Concomitantly, membrane-actin linker proteins ezrin-radixin-moesin (ERM) are recruited to the same membrane site via interaction with the intracellular domain of L1. We propose that the local regulation of the L1-ERM-actin pathway, at the level of the plasma membrane, underlies pGal-3-induced axon branching, and that galectin phosphorylation in situ could act as a molecular switch for the axon response to Gal-3.

show abstract

“…TG activity, which is found in the cytosol, plasma membrane, and nucleus of cells, has been implicated in a variety of physiological activities and pathological processes, including neuronal growth and regeneration (2)(3)(4), bone development (5-6), angiogenesis (7), wound healing (7), cellular differentiation, and apoptosis (8)(9)(10). During apoptosis, for example, TG-catalyzed crosslinking of proteins results in the irreversible formation of scaffolds that could prevent the leakage of harmful intracellular components (11).…”

mentioning

confidence: 99%

Structural basis for the guanine nucleotide-binding activity of tissue transglutaminase and its regulation of transamidation activity

Liu

Cerione

Clardy

2002

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

315

415

View full text Add to dashboard Cite

Tissue transglutaminase (TG) is a Ca 2؉ -dependent acyltransferase with roles in cellular differentiation, apoptosis, and other biological functions. In addition to being a transamidase, TG undergoes a GTP-binding͞GTPase cycle even though it lacks any obvious sequence similarity with canonical GTP-binding (G) proteins. Guanine nucleotide binding and Ca 2؉ concentration reciprocally regulate TG's transamidation activity, with nucleotide binding being the negative regulator. Here we report the x-ray structure determined to 2.8-Å resolution of human TG complexed with GDP. Although the transamidation active site is similar to those of other known transglutaminases, the guanine nucleotide-binding site of TG differs markedly from other G proteins. The structure suggests a structural basis for the negative regulation of transamidation activity by bound nucleotide, and the positive regulation of transamidation by Ca 2؉ .T issue transglutaminase (TG, also called type II transglutaminase) catalyzes the Ca 2ϩ -dependent formation of a new amide bond between the ␥-carboxamide of glutamine and the -amino group of lysine or another primary amine (1) (see scheme below).TG activity, which is found in the cytosol, plasma membrane, and nucleus of cells, has been implicated in a variety of physiological activities and pathological processes, including neuronal growth and regeneration (2-4), bone development (5-6), angiogenesis (7), wound healing (7), cellular differentiation, and apoptosis (8-10). During apoptosis, for example, TG-catalyzed crosslinking of proteins results in the irreversible formation of scaffolds that could prevent the leakage of harmful intracellular components (11). Retinoic acid (RA)-stimulated increases in TG expression and activation accompany RA-induced cellular differentiation (8,12). This increased TG expression, coupled with the finding that two of the primary targets for TG, the eukaryotic initiation factor eIF-5A and the retinoblastoma gene product (13,14), are essential for cell viability has led to the suggestion that TG activity is necessary for ensuring cell survival under conditions of differentiation or cellular stress. It has also been proposed that the dysregulation of TG activity may be associated with neurodegenerative conditions such as Alzheimer's disease and Huntington's disease (15-17).TG's ability to bind and hydrolyze GTP with affinity and rates like those of traditional G proteins distinguishes it from other transglutaminases and suggests that TG, like other G proteins, participates in signaling pathways (18)(19)(20)(21). Among the studies implicating TG as a signal transducer in biological response pathways, the best documented is its role in ␣1-adrenergic receptor-mediated stimulation of phospholipase C-␦ activity (21-23). It was originally reported that an Ϸ70-to 80-kDa GTP-binding protein (named Gh) was responsible for coupling ␣1-adrenergic agonists to the stimulation of phosphoinositide lipid metabolism (24), and it was subsequently demonstrated that Gh was identical to TG (21)....

show abstract

Stabilization of neurites in cerebellar granule cells by transglutaminase activity: identification of midkine and galectin-3 as substrates

Cited by 43 publications

References 74 publications

Tissue Transglutaminase Directly Regulates Adenylyl Cyclase Resulting in Enhanced cAMP-response Element-binding Protein (CREB) Activation

Tissue Transglutaminase Directly Regulates Adenylyl Cyclase Resulting in Enhanced cAMP-response Element-binding Protein (CREB) Activation

Phosphorylation of adhesion- and growth-regulatory human galectin-3 leads to the induction of axonal branching by local membrane L1 and ERM redistribution

Structural basis for the guanine nucleotide-binding activity of tissue transglutaminase and its regulation of transamidation activity

Contact Info

Product

Resources

About