Protein palmitoylation regulates extracellular vesicle production and function in sepsis

Yang, Xiaoyuan; Zheng, Ethan; Chatterjee, Victor; Ma, Yonggang; Reynolds, Amanda J.; Villalba, Nuria; Wu, Mack H.; Yuan, Sarah Y.

doi:10.1002/jex2.50

Cited by 1 publication

(1 citation statement)

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“…This is consistent with a proteomics study showing that a panel of palmitoylated proteins enriched into EVs is suppressed by a palmitoylation inhibitor (Mariscal et al., 2020 ). Similarly, the deficiency of DHHC21, a palmitoyl acyltransferase, significantly changed the protein profile in EVs (Yang et al., 2022 ). In particular, some palmitoylated proteins have been reported to favour encapsulation into EVs.…”

Section: Discussionmentioning

confidence: 99%

Src family kinases engage differential pathways for encapsulation into extracellular vesicles

Ye,

Gosser,

Runyon

et al. 2023

J of Extracellular Bio

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Extracellular vesicles (EVs) are heterogeneous biological nanoparticles secreted by all cell types. Identifying the proteins preferentially encapsulated in secreted EVs will help understand their heterogeneity. Src family kinases including Src and Fyn are a group of tyrosine kinases with fatty acylation modifications and/or multiple lysine residues (contributing charge interaction) at their N‐terminus. Here, we demonstrate that Src and Fyn kinases were preferentially encapsulated in EVs and fatty acylation including myristoylation and palmitoylation facilitated their encapsulation. Genetic loss or pharmacological inhibition of myristoylation suppressed Src and/or Fyn kinase levels in EVs. Similarly, loss of palmitoylation reduced Fyn levels in EVs. Additionally, mutation of lysine at sites 5, 7, and 9 of Src kinase also inhibited the encapsulation of myristoylated Src into EVs. Knockdown of TSG101, which is a protein involved in the endosomal sorting complexes required for transport (ESCRT) protein complex mediated EVs biogenesis and led to a reduction of Src levels in EVs. In contrast, filipin III treatment, which disturbed the lipid raft structure, reduced Fyn kinase levels, but not Src kinase levels in EVs. Finally, elevated levels of Src protein were detected in the serum EVs of host mice carrying constitutively active Src‐mediated prostate tumours in vivo. Collectively, the data suggest that different EVs biogenesis pathways exist and can regulate the encapsulation of specific proteins into EVs. This study provides an understanding of the EVs heterogeneity created by different EVs biogenesis pathways.

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Section: Discussionmentioning

confidence: 99%