scholarly journals Mutations in palmitoyl-protein thioesterase 1 alter exocytosis and endocytosis at synapses inDrosophilalarvae

Fly ◽  
2013 ◽  
Vol 7 (4) ◽  
pp. 267-279 ◽  
Author(s):  
Elizabeth Aby ◽  
Katherine Gumps ◽  
Amalia Roth ◽  
Stacey Sigmon ◽  
Sarah E Jenkins ◽  
...  
Keyword(s):  
Palmitoyl Protein Thioesterase

Developmental expression of palmitoyl protein thioesterase in normal mice

1999 ◽  
Vol 118 (1-2) ◽  
pp. 1-11 ◽  
Author(s):  
Juha Isosomppi ◽  
Outi Heinonen ◽  
Jukka O Hiltunen ◽  
Nicholas D.E Greene ◽  
Jouni Vesa ◽  
...  
Keyword(s):  
Developmental Expression ◽  
Palmitoyl Protein Thioesterase

How Antimalarials and Antineoplastic Drugs can Interact in Combination Therapies: a Perspective on the Role of PPT1 Enzyme

2021 ◽  
Vol 22 ◽  
Author(s):  
Diana Duarte ◽  
Nuno Vale
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Antineoplastic Agents ◽  
Antimalarial Drugs ◽  
Antineoplastic Drugs ◽  
Anticancer Effects ◽  
Different Types ◽  
Important Pathway ◽  
Palmitoyl Protein Thioesterase

: Antimalarial drugs from different classes have demonstrated anticancer effects in different types of cancer cells, but their complete mode of action in cancer remains unknown. Recently, several studies reported the important role of palmitoyl-protein thioesterase 1 (PPT1), a lysosomal enzyme, as the molecular target of chloroquine and its derivates in cancer. It was also found that PPT1 is overexpressed in different types of cancer, such as breast, colon, etc. Our group has found a synergistic interaction between antimalarial drugs, such as mefloquine, artesunate and chloroquine and antineoplastic drugs in breast cancer cells, but the mechanism of action was not determined. Here, we describe the importance of autophagy and lysosomal inhibitors in tumorigenesis and hypothesize that other antimalarial agents besides chloroquine could also interact with PPT1 and inhibit the mechanistic target of rapamycin (mTOR) signalling, an important pathway in cancer progression. We believe that PPT1 inhibition results in changes in the lysosomal metabolism that result in less accumulation of antineoplastic drugs in lysosomes, which increases the bioavailability of the antineoplastic agents. Taken together, these mechanisms help to explain the synergism of antimalarial and antineoplastic agents in cancer cells.

PPT1 Deficiency-Induced GABAAR Hyperpalmitoylation Impairs Synaptic Transmission And Memory Formation

2021 ◽  
Author(s):  
Jia Tong ◽  
Bingyan Feng ◽  
Jingjing Gao ◽  
Xing Zhao ◽  
Junmei Li ◽  
...  
Keyword(s):  
Neuronal Ceroid Lipofuscinosis ◽  
Immunofluorescent Staining ◽  
Electrophysiological Recording ◽  
Spatial Learning And Memory ◽  
Infantile Neuronal Ceroid Lipofuscinosis ◽  
Biochemical Assays ◽  
Behavioural Tests ◽  
Palmitoyl Protein Thioesterase ◽  
First Time

Abstract Background: Palmitoylation is a reversible and dynamic process involving addition of palmitic acid to cysteine residues of proteins. Studies have indicated that a variety of neuronal receptors, including glutamate receptors such as AMPAR, NMDAR, and GABAAR, are palmitoylated, which contributes to the dynamic modulation of synaptic strength in response to neuronal activity. However, little is known about the depalmitoylation of these receptors. Methods: A mouse model with a lost function mutation knock-in of palmitoyl protein thioesterase 1 (PPT1), an important enzyme for depalmitoylation, was employed to mimic human disease of infantile neuronal ceroid lipofuscinosis (INCLs). Immunofluorescent staining, Western blotting, biochemical assays, electrophysiological recording and behavioural tests were used to measure the effects of PPT1 deficiency.Results: We identified for the first time that the GABAARα1 subunit rather than AMPAR is the substrate of PPT1. In PPT1-deficient mice, excessive palmitoylation and extended membrane location of GABAAR were detected. Simultaneously, spatial learning and memory deficits with dysregulation of neuronal network γ oscillation and impairment of long-term plasticity were shown in the mice at as early as 2-month-old. Application of N-tert-butylhydroxylamine hydrochloride, a thioesterase mimetic, attenuated PPT1 mutation-induced GABAAR hyper-palmitoylation and its membrane accumulation with improved neuronal transmission and memory functions in the mice. Conclusions: These data provide new insights into the mechanisms of neuronal disorder caused by depalmitoylation deficiency and offer a clue for further intervention for INCLs and other neurodegenerative diseases.

Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis

Nature ◽  
1995 ◽  
Vol 376 (6541) ◽  
pp. 584-587 ◽  
Author(s):  
Jouni Vesa ◽  
Elina Hellsten ◽  
Linda A. Verkruyse ◽  
Laura A. Camp ◽  
Juhani Rapola ◽  
...  
Keyword(s):  
Neuronal Ceroid Lipofuscinosis ◽  
Infantile Neuronal Ceroid Lipofuscinosis ◽  
Ceroid Lipofuscinosis ◽  
Palmitoyl Protein Thioesterase

Characterization of Drosophila palmitoyl-protein thioesterase 1

Gene ◽  
2003 ◽  
Vol 312 ◽  
pp. 271-279 ◽  
Author(s):  
Robert L. Glaser ◽  
Anthony J. Hickey ◽  
Heather L. Chotkowski ◽  
Quynh Chu-LaGraff
Keyword(s):  
Palmitoyl Protein Thioesterase
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