Publications by authors named "Jairus M Reddy"

2 Publications

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Regulation of Small GTPase Prenylation in the Nervous System.

Mol Neurobiol 2020 May 27;57(5):2220-2231. Epub 2020 Jan 27.

Texas Woman's University, Denton, TX, USA.

Mevalonate pathway inhibitors have been extensively studied for their roles in cholesterol depletion and for inhibiting the prenylation and activation of various proteins. Inhibition of protein prenylation has potential therapeutic uses against neurological disorders, like neural cancers, neurodegeneration, and neurotramatic lesions. Protection against neurodegeneration and promotion of neuronal regeneration is regulated in large part by Ras superfamily small guanosine triphosphatases (GTPases), particularly the Ras, Rho, and Rab subfamilies. These proteins are prenylated to target them to cellular membranes. Prenylation can be specifically inhibited through altering the function of enzymes of the mevalonate pathway necessary for isoprenoid production and attachment to target proteins to elicit a variety of effects on neural cells. However, this approach does not address how prenylation affects a specific protein. This review focuses on the regulation of small GTPase prenylation, the different techniques to inhibit prenylation, and how this inhibition has affected neural cell processes.
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http://dx.doi.org/10.1007/s12035-020-01870-0DOI Listing
May 2020

Non-prenylatable, cytosolic Rac1 alters neurite outgrowth while retaining the ability to be activated.

Cell Signal 2015 Mar 2;27(3):630-7. Epub 2014 Dec 2.

Texas Woman's University Department of Biology, Denton, TX 76204-5799, United States. Electronic address:

Rac1 is an important regulator of axon extension, cell migration and actin reorganization. Like all Rho guanine triphosphatases (GTPases), Rac1 is targeted to the membrane by the addition of a geranylgeranyl moiety, an action thought to result in Rac1 guanosine triphosphate (GTP) binding. However, the role that Rac1 localization plays in its activation (GTP loading) and subsequent activation of effectors is not completely clear. To address this, we developed a non-prenylatable emerald green fluorescent protein (EmGFP)-Rac1 fusion protein (EmGFP-Rac1(C189A)) and assessed how expressing this construct affected neurite outgrowth, Rac1 localization and activation in neuroblastoma cells. Expression of EmGFP-Rac1(C189A) increased localization to the cytosol and induced cell clustering while increasing neurite initiation. EmGFP-Rac1(C189A) expression also increased Rac1 activation in the cytosol, compared to cells expressing wild-type Rac1 (EmGFP-Rac1). These results suggest that activation of Rac1 may not require plasma membrane localization, potentially leading to differential activation of cytosolic signaling pathways that alter cell morphology. Understanding the consequences of differential localization and activation of Rho GTPases, including Rac1, could lead to new therapeutic targets for treating neurological disorders.
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http://dx.doi.org/10.1016/j.cellsig.2014.11.033DOI Listing
March 2015