Microcephaly protein ANKLE2 promotes Zika virus replication

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

ABSTRACT Orthoflaviviruses are positive-sense single-stranded RNA viruses that hijack host proteins to promote their own replication. Zika virus (ZIKV) is infamous among orthoflaviviruses for its association with severe congenital birth defects, notably microcephaly. We previously mapped ZIKV-host protein interactions and identified the interaction between ZIKV non-structural 4A (NS4A) microcephaly ankyrin repeat LEM domain-containing 2 (ANKLE2). Using a fruit fly model, we showed NS4A induced in an ANKLE2-dependent manner. Here, explore role of ANKLE2 replication understand biological significance from viral perspective. observe localization drastically shifted sites accumulation during infection knockout reduces multiple human cell lines. This decrease coupled moderate increase innate immune activation. microscopy, dysregulated formation virus-induced endoplasmic reticulum rearrangements cells. Knockdown ortholog Aedes aegypti cells also decreases replication, suggesting beneficial factor across hosts. Finally, show four other physically interacts Thus, likely promotes orthoflavivirus by regulating membrane serve accelerate genome protect dsRNA detection. Taken together our previous results, findings indicate conserved this drives unique pathogenesis since has essential roles developing tissues. IMPORTANCE major concern due including physical ANKLE2. Mutations cause microcephaly, induces establish Depletion significantly disrupts rearrangements. ANKLE2’s ability mosquito related mosquito-borne orthoflaviviruses. Our data point overall model which regulates avoid However, NS4A-induced consequence important tissues roles.

Language: Английский

---

Mechanisms of PP2A-Ankle2 dependent nuclear reassembly after mitosis

Published: Jan. 23, 2025

In animals, mitosis involves the breakdown of nucleus. The reassembly a nucleus after requires reformation nuclear envelope around single mass chromosomes. This process Ankle2 (also known as LEM4 in humans) which interacts with PP2A and promotes function Barrier-to-Autointegration Factor (BAF). Upon dephosphorylation, BAF dimers cross-bridge chromosomes bind lamins transmembrane proteins reassembling envelope. How functions is incompletely understood. Using combination approaches Drosophila , along structural modeling, we provide several lines evidence that suggest regulatory subunit PP2A, explaining how it dephosphorylation. addition, discovered endoplasmic reticulum protein Vap33, required for localization at during telophase. We identified interaction sites Vap33 on Ankle2. Through genetic rescue experiments, show Ankle2/PP2A essential Ankle2/Vap33 also this process. Our study sheds light molecular mechanisms post-mitotic suggests not merely source membranes process, but provides localized enzymatic activity.

Language: Английский

---

Mechanisms of PP2A-Ankle2 dependent nuclear reassembly after mitosis

eLife, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 18, 2025

In animals, mitosis involves the breakdown of nucleus. The reassembly a nucleus after requires reformation nuclear envelope around single mass chromosomes. This process Ankle2 (also known as LEM4 in humans) which interacts with PP2A and promotes function Barrier-to-Autointegration Factor (BAF). Upon dephosphorylation, BAF dimers cross-bridge chromosomes bind lamins transmembrane proteins reassembling envelope. How functions is incompletely understood. Using combination approaches Drosophila , along structural modeling, we provide several lines evidence that suggest regulatory subunit PP2A, explaining how it dephosphorylation. addition, discovered endoplasmic reticulum protein Vap33, required for localization at during telophase. We identified interaction sites Vap33 on Ankle2. Through genetic rescue experiments, show Ankle2/PP2A essential Ankle2/Vap33 also this process. Our study sheds light molecular mechanisms post-mitotic suggests not merely source membranes process, but provides localized enzymatic activity.

Language: Английский

---

Mechanisms of PP2A-Ankle2 dependent nuclear reassembly after mitosis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 7, 2024

ABSTRACT In animals, mitosis involves the breakdown of nucleus. The reassembly a nucleus after requires reformation nuclear envelope around single mass chromosomes. This process Ankle2 which interacts with PP2A and promotes function Barrier-to-Autointegration Factor (BAF). Upon dephosphorylation, BAF dimers cross-bridge chromosomes bind lamins transmembrane proteins reassembling envelope. How functions in is incompletely understood. Using combination approaches Drosophila , along structural modeling, we show for first time that regulatory subunit PP2A, explaining how it dephosphorylation. addition, discovered endoplasmic reticulum protein Vap33, required localization at during telophase. We identified interaction sites Vap33 on Ankle2. Through genetic rescue experiments, Ankle2/PP2A essential Ankle2/Vap33 also this process. Our study sheds light molecular mechanisms post-mitotic suggests not merely source membranes process, but provides localized enzymatic activity.

Language: Английский

---

Mechanisms of PP2A-Ankle2 dependent nuclear reassembly after mitosis

eLife, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 27, 2024

In animals, mitosis involves the breakdown of nucleus. The reassembly a nucleus after requires reformation nuclear envelope around single mass chromosomes. This process Ankle2 (also known as LEM4 in humans) which interacts with PP2A and promotes function Barrier-to-Autointegration Factor (BAF). Upon dephosphorylation, BAF dimers cross-bridge chromosomes bind lamins transmembrane proteins reassembling envelope. How functions is incompletely understood. Using combination approaches Drosophila , along structural modeling, we provide several lines evidence that suggest regulatory subunit PP2A, explaining how it dephosphorylation. addition, discovered endoplasmic reticulum protein Vap33, required for localization at during telophase. We identified interaction sites Vap33 on Ankle2. Through genetic rescue experiments, show Ankle2/PP2A essential Ankle2/Vap33 also this process. Our study sheds light molecular mechanisms post-mitotic suggests not merely source membranes process, but provides localized enzymatic activity.

Language: Английский

---

Mechanisms of PP2A-Ankle2 dependent nuclear reassembly after mitosis

Published: Nov. 27, 2024

In animals, mitosis involves the breakdown of nucleus. The reassembly a nucleus after requires reformation nuclear envelope around single mass chromosomes. This process Ankle2 which interacts with PP2A and promotes function Barrier-to-Autointegration Factor (BAF). Upon dephosphorylation, BAF dimers cross-bridge chromosomes bind lamins transmembrane proteins reassembling envelope. How functions in is incompletely understood. Using combination approaches Drosophila , along structural modeling, we show for first time that regulatory subunit PP2A, explaining how it dephosphorylation. addition, discovered endoplasmic reticulum protein Vap33, required localization at during telophase. We identified interaction sites Vap33 on Ankle2. Through genetic rescue experiments, Ankle2/PP2A essential Ankle2/Vap33 also this process. Our study sheds light molecular mechanisms post-mitotic suggests not merely source membranes process, but provides localized enzymatic activity.

Language: Английский

---