prikaz prve stranice dokumenta TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities
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TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities
The American Journal of Human Genetics, 105 (2019), 6; 1126-1147. https://doi.org/10.1016/j.ajhg.2019.10.009
Vandervore, Laura V.; ...; Milošević, Nataša Jovanov; ...

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Vandervore, L. V. i Milošević, N. J. (2019). TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities. The American Journal of Human Genetics, 105. (6), 1126-1147. doi: 10.1016/j.ajhg.2019.10.009

Vandervore, Laura V. i Nataša Jovanov Milošević. "TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities." The American Journal of Human Genetics, vol. 105, br. 6, 2019, str. 1126-1147. https://doi.org/10.1016/j.ajhg.2019.10.009

Vandervore, Laura V. i Nataša Jovanov Milošević. "TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities." The American Journal of Human Genetics 105, br. 6 (2019): 1126-1147. https://doi.org/10.1016/j.ajhg.2019.10.009

Vandervore, L. V. i Milošević, N. J. (2019) 'TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities', The American Journal of Human Genetics, 105(6), str. 1126-1147. doi: 10.1016/j.ajhg.2019.10.009

Vandervore LV, Milošević NJ. TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities. The American Journal of Human Genetics [Internet]. 05.12.2019. [pristupljeno 22.01.2025.];105(6):1126-1147. doi: 10.1016/j.ajhg.2019.10.009

L. V. Vandervore i N. J. Milošević, "TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities", The American Journal of Human Genetics, vol. 105, br. 6, str. 1126-1147, Prosinac 2019. [Online]. Dostupno na: https://urn.nsk.hr/urn:nbn:hr:105:093095. [Citirano: 22.01.2025.]

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Naslov (engleski)TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities
AutorLaura V. Vandervore
Autor
...
AutorNataša Jovanov Milošević
Autor
...
Autorova ustanovaSveučilište u Zagrebu
Medicinski fakultet
(HRVATSKI INSTITUT ZA ISTRAŽIVANJE MOZGA)
Autorova ustanovaSveučilište u Zagrebu
Medicinski fakultet
(KATEDRA ZA MEDICINSKU BIOLOGIJU)
Znanstveno / umjetničko
područje, polje i grana		BIOMEDICINA I ZDRAVSTVO
Kliničke medicinske znanosti
Klinička citologija
Znanstveno / umjetničko
područje, polje i grana		BIOMEDICINA I ZDRAVSTVO
Kliničke medicinske znanosti
Neurologija
Sažetak (engleski)
The redox state of the neural progenitors regulates physiological processes such as neuronal differentiation and dendritic and axonal growth. The relevance of endoplasmic reticulum (ER)-associated oxidoreductases in these processes is largely unexplored. We describe a severe neurological disorder caused by bi-allelic loss-of-function variants in thioredoxin (TRX)-related transmembrane-2 (TMX2); these variants were detected by exome sequencing in 14 affected individuals from ten unrelated families presenting with congenital microcephaly, cortical polymicrogyria, and other migration disorders. TMX2 encodes one of the five TMX proteins of the protein disulfide isomerase family, hitherto not linked to human developmental brain disease. Our mechanistic studies on protein function show that TMX2 localizes to the ER mitochondria-associated membranes (MAMs), is involved in posttranslational modification and protein folding, and undergoes physical interaction with the MAM-associated and ER folding chaperone calnexin and ER calcium pump SERCA2. These interactions are functionally relevant because TMX2-deficient fibroblasts show decreased mitochondrial respiratory reserve capacity and compensatory increased glycolytic activity. Intriguingly, under basal conditions TMX2 occurs in both reduced and oxidized monomeric form, while it forms a stable dimer under treatment with hydrogen peroxide, recently recognized as a signaling molecule in neural morphogenesis and axonal pathfinding. Exogenous expression of the pathogenic TMX2 variants or of variants with an in vitro mutagenized TRX domain induces a constitutive TMX2 polymerization, mimicking an increased oxidative state. Altogether these data uncover TMX2 as a sensor in the MAM-regulated redox signaling pathway and identify it as a key adaptive regulator of neuronal proliferation, migration, and organization in the developing brain.
Ključne riječi (engleski)
Jezikengleski
Vrsta publikacijeZnanstveni rad - Izvorni znanstveni rad
Status objaveObjavljen
Vrsta recenzijeRecenziran
Verzija publikacijeObjavljena verzija rada (izdavačev PDF)
Naslov časopisaThe American Journal of Human Genetics
Brojčani podacivol. 105, br. 6, str. 1126-1147
p-ISSN0002-9297
e-ISSN1537-6605
DOIhttps://doi.org/10.1016/j.ajhg.2019.10.009
URN:NBNurn:nbn:hr:105:093095
Datum objave publikacije2019-12-05
URL dokumentahttps://linkinghub.elsevier.com/retrieve/pii/S0002929719303970
Vrsta resursaTekst
Prava pristupaOtvoreni pristup
Uvjeti korištenjaIkona licence Zaštićeno autorskim pravom.
Datum i vrijeme pohrane2021-01-12 10:16:35