Insights into the pathogenesis of primary hyperoxaluria type I from the structural dynamics of alanine:glyoxylate aminotransferase variants
Mutations in alanine:glyoxylate aminotransferase (AGT) leading to protein misfolding cause primary hyperoxaluria type I (PH1). Here, we use hydrogen-deuterium exchange to characterize the structural dynamics of AGT variants. These dynamics are heterogeneously distributed across the structure and different functional sites. Disease-associated variants show local destabilization. Our work provides novel insight into the pathogenic mechanisms causing PH1. Primary hyperoxaluria type I (PH1) is caused by deficient alanine:glyoxylate aminotransferase (AGT) activity. PH1-causing mutations in AGT lead to protein mistargeting and a...
Source: FEBS Letters - February 27, 2024 Category: Biochemistry Authors: Pavla Vankova, Juan Luis Pacheco ‐Garcia, Dmitry S. Loginov, Atanasio Gómez‐Mulas, Alan Kádek, José Manuel Martín‐Garcia, Eduardo Salido, Petr Man, Angel L. Pey Tags: Research Article Source Type: research

A ‐kinase anchoring proteins are enriched in the central pair microtubules of motile cilia in Chlamydomonas reinhardtii
Effective motile cilia beating demands intricate coordination of various ciliary components, including proteins of the scaffold, radial spoke, and central pair. Among the scaffold proteins, A-kinase anchoring proteins (AKAPs) play a pivotal role. Thus far, the identity of central pair AKAPs has remained elusive. In our current study, we employed a blend of biochemical/biophysical methods to unveil three central pair AKAPs by utilizing an AKAP-interacting protein, FAP174, as a bait. Cilia are microtubule-based sensory organelles present in a number of eukaryotic cells. Mutations in the genes encoding ciliary proteins cause ...
Source: FEBS Letters - February 27, 2024 Category: Biochemistry Authors: Venkatramanan G. Rao, Amruta A. Shendge, Percival P. D'Gama, Elvis A. F. Martis, Shraddha Mehta, Evans C. Coutinho, Jacinta S. D'Souza Tags: Research Article Source Type: research

Mdm2 ‐mediated ubiquitination of PKCβII is responsible for insulin‐induced heterologous desensitization of dopamine D3 receptor
In response to insulin stimulation, the E3 ligase enzyme Mdm2 exits the nucleus and interacts with PKC βII, facilitating the ubiquitination of PKCβII. Subsequently, the ubiquitinated PKCβII translocates to the cell membrane and associates with D3R, resulting in the inhibition of D3R cAMP signaling and linking it to clathrin-mediated endocytosis and degradation. The insulin and dopaminergic systems in the brain are associated with schizophrenia and Parkinson's disease with respect to etiology and treatment. The present study investigated the crosstalk between the insulin receptor (IR) and dopamine receptor and found that...
Source: FEBS Letters - February 27, 2024 Category: Biochemistry Authors: Xingyue Zeng, ChengYan Wu, Yongkai Cao, Huijun Li, Xiaohan Zhang Tags: Research Article Source Type: research

Osmotic stress induces the formation of migrasome ‐like vesicles
In this study, we report the formation of migrasome-like vesicles enriched in tetraspanin 4 and containing cytoplasmic components in response to hypoosmotic stress. When migrating cells were subjected to hypoosmotic stress, vesicles with a size distribution of 0.5 to 2  μm formed on the retraction fibers, and vanished in a few minutes. The vesicles are rich in cholesterol, and their number was reduced when cells were pretreated with lipoprotein-deficient serum. The formation of migrasome-like vesicles upon hypoosmotic stress may provide biophysical cues regardi ng the cellular response to this external stimulus in cells...
Source: FEBS Letters - February 27, 2024 Category: Biochemistry Authors: Koki Yoshikawa, Shogo Saito, Tetsuya Kadonosono, Masayoshi Tanaka, Mina Okochi Tags: Research Letter Source Type: research

The lipid ‐binding D4 domain of perfringolysin O facilitates the active loading of exogenous cargo into extracellular vesicles
This study investigates the role of domain 4 (D4), a cholesterol-binding domain as a viable candidate for extracellular vesicle (EV) protein loading and cargo delivery. D4 recognizes cholesterol in the EV membrane and recruits proteins of interest into EVs. Our experiments using split-nano luciferase technology enhanced by fusogenic vesicular stomatitis virus glycoprotein also demonstrate the capability of D4-engineered EVs for intracellular protein delivery. Whereas extracellular vesicles (EVs) have been engineered for cargo loading, innovative strategies for it can still be developed. Here, we describe domain 4 (D4), a c...
Source: FEBS Letters - February 27, 2024 Category: Biochemistry Authors: Abayomi Emmanuel Opadele, Soichiro Nishioka, Ping ‐Hsiu Wu, Quynh‐Thu Le, Hiroki Shirato, Jin‐Min Nam, Yasuhito Onodera Tags: Research Letter Source Type: research

Akt may associate with insulin ‐responsive vesicles via interaction with sortilin
Insulin-responsive vesicles (IRVs) are formed by self-assembly of Glut4, sortilin, insulin-responsive amino peptidase (IRAP), and low-density lipoprotein receptor-related protein 1 (LRP1). TBC1D4 in the insulin signaling pathway binds to the cytoplasmic tails of IRAP and LRP. Here, we demonstrate that the insulin signaling protein Akt interacts with the cytoplasmic tail of sortilin. We suggest that the IRVs represent a scaffold for the final steps of insulin action. Insulin-responsive vesicles (IRVs) deliver the glucose transporter Glut4 to the plasma membrane in response to activation of the insulin signaling cascade: ins...
Source: FEBS Letters - February 27, 2024 Category: Biochemistry Authors: Nava Zaarur, Anatoli B. Meriin, Maneet Singh, Raghuveera K. Goel, Joseph Zaia, Konstantin V. Kandror Tags: Research Letter Source Type: research

Cell competition: emerging signaling and unsolved questions
Cell competition is a form of cell –cell interaction whereby cells with higher fitness (“winners”) actively eliminate neighboring less-fit cells (“losers”) in the growing tissue. In this review, we summarize and discuss emerging signaling mechanisms and critical unsolved questions in cell competition. Multicellular communities have an intrinsic mechanism that optimizes their structure and functionvia cell –cell communication. One of the driving forces for such self-organization of the multicellular system is cell competition, the elimination of viable unfit or deleterious cellsvia cell –cell interaction. Stud...
Source: FEBS Letters - February 27, 2024 Category: Biochemistry Authors: Rina Nagata, Tatsushi Igaki Tags: Review Source Type: research

Front Cover
Cover illustration Formation of migrasome-like vesicles in H4/TSPAN4-sfGFP/mCherry cells subjected to hypoosmotic stress. The image refers to Yoshikawa et al. ‘Osmotic stress induces the formation of migrasome-like vesicles’. (Source: FEBS Letters)
Source: FEBS Letters - February 27, 2024 Category: Biochemistry Tags: Issue Information Source Type: research

Interlinked bi ‐stable switches govern the cell fate commitment of embryonic stem cells
Nanog and Oct4 are the key regulatory genes that govern the developmental dynamics of embryonic stem cells to trophectoderm and primitive endoderm by maintaining specific steady-state expression patterns. Herein, we hypothesize stepwise switching and mushroom-like bifurcation dynamics for Oct4 and Nanog, respectively, that align well with the existing experimental findings and shed light on fate-determination events. The development of embryonic stem (ES) cells to extraembryonic trophectoderm and primitive endoderm lineages manifests distinct steady-state expression patterns of two key transcription factors —Oct4 and Nan...
Source: FEBS Letters - February 27, 2024 Category: Biochemistry Authors: Amitava Giri, Sandip Kar Tags: Research Article Source Type: research

Probing the legitimate initiation of RNA synthesis by Q β replicase with oligonucleotide primers
An oligonucleotide shorter than the distance to the nearest template hairpin can initiate RNA synthesis on a legitimate Q β replicase template. The optimal primer length varies for different templates. The primer binding is greatly stabilized by its 5′-triphosphate group and Mg2+ ions. Oligoribonucleotides complementary to the template 3 ′ terminus were tested for their ability to initiate RNA synthesis on legitimate templates capable of exponential amplification by Qβ replicase. Oligonucleotides shorter than the distance to the nearest predicted template hairpin proved able to serve as primers, with the optimal leng...
Source: FEBS Letters - February 27, 2024 Category: Biochemistry Authors: Kirill V. Lobodin, Helena V. Chetverina, Alexander B. Chetverin Tags: Research Letter Source Type: research

Protein sorting upon exit from the endoplasmic reticulum dominates Golgi biogenesis in budding yeast
The endoplasmic reticulum (ER) serves not only as a site of coat protein complex II vesicle formation but also as a site of protein sorting in budding yeast. Our data show that mutant strains defective in protein sorting in the ER affect the numbers of Golgi cisternae. This finding suggests that protein sorting plays a critical role in maintaining Golgi biogenesis. Cells sense and control the number and quality of their organelles, but the underlying mechanisms of this regulation are not understood. Our recent research in the yeastSaccharomyces cerevisiae has shown that long acyl chain ceramides in the endoplasmic reticulu...
Source: FEBS Letters - February 24, 2024 Category: Biochemistry Authors: Saku Sasaki, Philipp Schlarmann, Kazuki Hanaoka, Hinako Nishii, Hisao Moriya, Manuel Mu ñiz, Kouichi Funato Tags: Research Letter Source Type: research