Bro1 family proteins harmonize cargo sorting with vesicle formation

Tseng, Chun-Che; Piper, Robert C.; Katzmann, David J.

doi:10.1002/bies.202100276

Cited by 4 publications

(2 citation statements)

References 108 publications

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“…ALIX (ALG-2-interacting protein X) is a multifunctional protein containing the Bro1 domain ( Figure 3 A) [ 175 , 176 ]. ALIX was found to be one of the most reliable protein markers of exosomes [ 177 ].…”

Section: Exosome Loading With Tnasmentioning

confidence: 99%

Extracellular Vesicles for Therapeutic Nucleic Acid Delivery: Loading Strategies and Challenges

Oshchepkova

Zenkova

Vlassov

2023

IJMS

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Extracellular vesicles (EVs) are membrane vesicles released into the extracellular milieu by cells of various origins. They contain different biological cargoes, protecting them from degradation by environmental factors. There is an opinion that EVs have a number of advantages over synthetic carriers, creating new opportunities for drug delivery. In this review, we discuss the ability of EVs to function as carriers for therapeutic nucleic acids (tNAs), challenges associated with the use of such carriers in vivo, and various strategies for tNA loading into EVs.

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Section: Exosome Loading With Tnasmentioning

confidence: 99%

Extracellular Vesicles for Therapeutic Nucleic Acid Delivery: Loading Strategies and Challenges

Oshchepkova

Zenkova

Vlassov

2023

IJMS

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“…These Bro1 Domain family members also function later during ESCRT-mediated processes through 1) promoting ESCRT-III assembly via activating CHMP4/Snf7 [40,55,56], 2) recruiting ubiquitin isopeptidases to recycle ubiquitin from cargo [52,[57][58][59][60], and 3) facilitating ESCRT-III-driven membrane remodeling by activating the Vps4 ATPase [48,61]. These varied activities position Bro1 Domain family members as critical factors regulating ESCRT-driven processes [62]. HD-PTP and ALIX mediate distinct ESCRT processes.…”

Section: Introductionmentioning

confidence: 99%

HD-PTP/PTPN23 hypomorphic mice display lipodystrophy

Davies¹,

Payne²,

Martin³

et al. 2022

Preprint

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Endosomal Sorting Complexes Required for Transport (ESCRTs) drive reverse topology membrane remodeling events including the formation of intralumenal vesicles within multivesicular bodies, the budding of retroviruses from the plasma membrane, and the scission of the cytokinetic bridge. It has been difficult to study the physiological relevance of this machinery in mammals because many contributing components are essential for viability. To bypass this problem we used combinations of knockout (−), hypomorphic (H) and wildtype (+) alleles to generate a series of mice with a gradual reduction of HD-PTP (product of PTPN23), an ESCRT-associated protein known to cause embryonic lethality when fully depleted. Whereas PTPN23−/H mice died shortly after birth, PTPN23H/H mice developed into adulthood but had reduced size, lipodystrophy, and shortened lifespan. Analysis of 14-day inguinal adipose tissue indicated reduced expression of adipogenesis markers, and PTPN23 knockout preadipocytes similarly display reduced adipogenesis in vitro. Defects in insulin-stimulated signaling were apparent in differentiated PTPN23 knockout adipocytes and PTPN23H/H inguinal adipose tissue in vitro, correlating with reduced levels of insulin signaling hallmarks observed in adult PTPN23H/H inguinal adipose tissue in vivo. Whereas the ESCRT machinery have been suggested to downregulate signaling, these results indicate that HD-PTP promotes insulin-induced signaling in, as well as differentiation of, inguinal adipose tissue. These results revealed unexpected roles for HD-PTP in promoting fat accumulation in mammalian cells through supporting insulin signaling, adipogenesis, and lipid droplet formation.

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