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 - December 18, 2023 Category: Biochemistry Authors: Nava Zaarur, Anatoli B. Meriin, Maneet Singh, Raghuveera K. Goel, Joseph Zaia, Konstantin V. Kandror Tags: Research Letter Source Type: research

The autophagy of stress granules
Numerous links exist between stress granules (SGs) and neurodegenerative disease. When SGs cannot be properly cleared from the cell, they may become pathological and promote the aggregation of neurotoxic proteins. It is thus crucial that we understand the precise processes governing the degradation of SGs. Autophagy is a major mechanism mediating SGs clearance, and autophagy dysfunction is a cardinal feature of neurodegenerative disease. In this review, we summarise current knowledge regarding the autophagy of SGs. Our understanding of stress granule (SG) biology has deepened considerably in recent years, and with this inc...
Source: FEBS Letters - December 16, 2023 Category: Biochemistry Authors: Laura Ryan, David C. Rubinsztein Tags: In a Nutshell Source Type: research

Autophagy as an innate immunity response against pathogens: a Tango dance
A bacterium and an autophagosome illustrated as dancing aTango. This dance mirrors how autophagy and intracellular pathogens interact. (A) In specific instances, the autophagosome closely interacts with the partner, embracing the bacterium for engulfment and subsequent delivery into lysosomes for degradation. (B) In other cases, the bacterium responds and escapes from (avoid) the leader partner. These illustrations were created by Dr. Diego Croci, Group Leader at IHEM, CONICET, Argentina. Intracellular infections as well as changes in the cell nutritional environment are main events that trigger cellular stress responses. ...
Source: FEBS Letters - December 16, 2023 Category: Biochemistry Authors: Milton O. Aguilera, Laura R. Delgui, Fulvio Reggiori, Patricia S. Romano, Mar ía I. Colombo Tags: Review Source Type: research

Front Cover
Cover illustration 3D organisation of the thylakoid stacks that shows the three continuous phases: the lumen (light green), the bilayer membrane (dark green) and the stroma. The cover refers to Launayet al. ‘Location of the photosynthetic carbon metabolism in microcompartments and separatedphases in microalgal cells’ (in this issue). Image taken from Engelet al. (2015). Native architecture of theChlamydomonas chloroplast revealed by in situ cryo –electron tomographyeLife 4:e04889. (Source: FEBS Letters)
Source: FEBS Letters - December 12, 2023 Category: Biochemistry Tags: Issue Information Source Type: research

Intrinsic disorder of a nucleoplasmin ‐like histone chaperone specifies its discrete nuclear and nucleolar functions
All nucleoplasmin (NPM) proteins have large regions of intrinsic disorder, but it is not clear whether intrinsic disorder is an absolute requirement for all functions attributed to NPMs. We show that disordered regions of a yeast NPM-like protein, and lysine polyphosphorylation sites within them, are dispensable for NPM nucleolar functions, but key to NPM-mediated gene repression in the nucleus. Nucleoplasmin (NPM) histone chaperones regulate distinct processes in the nucleus and nucleolus. While intrinsically disordered regions (IDRs) are hallmarks of NPMs, it is not clear whether all NPM functions require these unstructu...
Source: FEBS Letters - December 11, 2023 Category: Biochemistry Authors: Courtney M. Gauthier, Josey LeGallais, Neda Savic, Sarah Moradi ‐Fard, Arden Grew, Martin Loe, Baran Kirlikaya, Jennifer Cobb, Christopher J. Nelson Tags: Research Letter Source Type: research

Intrinsic disorder of a nucleoplasmin ‐like histone chaperone specifies its discrete nuclear and nucleolar functions
All nucleoplasmin (NPM) proteins have large regions of intrinsic disorder, but It is not clear if intrinsic disorder is an absolute requirement for all functions attributed to NPMs. We show that disordered regions of a yeast NPM-like protein, and lysine polyphosphorylation sites within them, are dispensable for NPM nucleolar functions, but key to NPM-mediated gene repression in the nucleus. Nucleoplasmin (NPM) histone chaperones regulate distinct processes in the nucleus and nucleolus. While intrinsically disordered regions (IDRs) are hallmarks of NPMs, it is not clear if all NPM functions require these unstructured featur...
Source: FEBS Letters - December 7, 2023 Category: Biochemistry Authors: Courtney M. Gauthier, Josey LeGallais, Neda Savic, Sarah Moradi ‐Fard, Arden Grew, Martin Loe, Baran Kirlikaya, Jennifer Cobb, Christopher J. Nelson Tags: Research Letter Source Type: research

Human WIPI β‐propeller function in autophagy and neurodegeneration
Human WIPI β-propellers fulfill important functions in autophagy as phosphatidylinositol 3-phosphate effectors. The underlying scaffolding function is physiologically essential as WIPI mutations have dramatic effects on human health, particularly causing neurodegenerative diseases. The connection between WIPI mutations (A), the process of autophagy (B) and the neurodegenerative diseases (C) caused by WIPI mutations is given special attention in this review. The four human WIPI β-propellers, WIPI1 through WIPI4, belong to the ancient PROPPIN family and fulfill scaffold functions in the control of autophagy. In this contex...
Source: FEBS Letters - December 7, 2023 Category: Biochemistry Authors: Tassula Proikas ‐Cezanne, Maximilian L. Haas, Carmen J. Pastor‐Maldonado, David S. Schüssele Tags: In a Nutshell Source Type: research

Nonenzymatic RNA replication in a mixture of ‘spent’ nucleotides
In this study, we characterised the effect of a mixture of ‘spent’ nucleotides on template-directed nonenzymatic RNA replication, to understand how they might affect the reaction rates. Nonenzymatic template-directed replication would have been affected by co-solutes in a heterogenous prebiotic soup due to lack of enzymatic machinery. Unlike in contemporary biology, these reactions use chemically-activated nucleotides, which undergo rapid hydrolysis forming nucleoside monophosphates ( ‘spent’ monomers). These co-solutes cannot extend the primer but continue to base pair with the template, thereby interfering with r...
Source: FEBS Letters - December 7, 2023 Category: Biochemistry Authors: Gauri M. Patki, Sudha Rajamani Tags: Research Article Source Type: research

Human mitochondrial uncoupling protein 3 functions as a metabolite transporter
We show that recombinant human uncoupling protein 3 (UCP3), refolded and reconstituted into liposomes, efficiently transports aspartate and malate, and, to a lesser extent, phosphate and sulphate. Unlike UCP2, UCP3 cannot catalyse unidirectional substrate transport and exhibits an approximately sevenfold higher transport affinity for aspartate compared to UCP2. The R282Q mutation in the sixth α-helix completely abolishes the transport activity of UCP3. Since its discovery, a major debate about mitochondrial uncoupling protein 3 (UCP3) has been whether its metabolic actions result primarily from mitochondrial inner membran...
Source: FEBS Letters - December 7, 2023 Category: Biochemistry Authors: Francesco De Leonardis, Amer Ahmed, Angelo Vozza, Loredana Capobianco, Christopher L. Riley, Simona Nicole Barile, Daria Di Molfetta, Stefano Tiziani, John DiGiovanni, Luigi Palmieri, Vincenza Dolce, Giuseppe Fiermonte Tags: Research Letter Source Type: research

CRK and NCK adaptors may functionally overlap in zebrafish neurodevelopment, as indicated by common binding partners and overlapping expression patterns
This study finds CRK and NCK adaptors overlap in their neuronal expression during zebrafish development. It also finds CRK and NCK adaptors share common SH2 and SH3 binding partners from a neuronal cell line. Common binding partners include proteins critical for cell motility and adhesion. Together these data suggest CRK and NCK adaptors can play overlapping roles in neurodevelopment. CRK adaptor proteins are important for signal transduction mechanisms driving cell proliferation and positioning during vertebrate central nervous system development. Zebrafish lacking both CRK family members exhibit small, disorganized retin...
Source: FEBS Letters - December 7, 2023 Category: Biochemistry Authors: Helaina R. Stergas, Maeve Dillon ‐Martin, Caroline M. Dumas, Nicole A. Hansen, Francesca J. Carasi‐Schwartz, Alex R. D’Amico, Kylie M. Finnegan, Uatchet Juch, Keeley R. Kane, Isabel E. Kaplan, Madeline L. Masengarb, Marina E. Melero, Lau Tags: Research Article Source Type: research

Chemokine N ‐terminal‐derived peptides differentially regulate signaling by the receptors CCR1 and CCR5
In conclusion, chemokin e N termini can be mimicked to produce small CCR1-selective agonists, as well as CCR5-selective modulators. (Source: FEBS Letters)
Source: FEBS Letters - December 6, 2023 Category: Biochemistry Authors: Olav Larsen, Sara Schuermans, Anna Walser, Stavroula Louka, Ida Aaberg Lillethorup, Jon V åbenø, Katrine Qvortrup, Paul Proost, Mette M. Rosenkilde Tags: Research Letter Source Type: research

Gly56 in the synthetic site of isoleucyl ‐tRNA synthetase confers specificity and maintains communication with the editing site
Isoleucyl-tRNA synthetase (IleRS) is crucial for isoleucine decoding in every cell. How IleRS discriminates against the smaller valine, preserving the accuracy of translation, is an important question. Here, we show that the strictly conserved Gly is a key for amino acid discrimination in synthetic site-based editing reactions. Interestingly, Gly, located in the synthetic site, modulates the affinity of the distant editing site. Isoleucyl-tRNA synthetase (IleRS) links isoleucine to cognate tRNAvia the Ile-AMP intermediate. Non-cognate valine is often mistakenly recognized as the IleRS substrate; therefore, to maintain the ...
Source: FEBS Letters - December 6, 2023 Category: Biochemistry Authors: Morana Dulic, Nina Krpan, Ita Gruic ‐Sovulj Tags: Research Article Source Type: research

Human mitochondrial uncoupling protein 3 functions as a metabolite transporter
We show that recombinant human uncoupling protein 3 (UCP3), refolded and reconstituted into liposomes, efficiently transports aspartate and malate, and, to a lesser extent, phosphate and sulphate. Unlike UCP2, UCP3 cannot catalyse unidirectional substrate transport and exhibits an approximately sevenfold higher transport affinity for aspartate compared to UCP2. The R282Q mutation in the sixth α-helix completely abolishes the transport activity of UCP3. Since its discovery, a major debate about mitochondrial uncoupling protein 3 (UCP3) has been whether its metabolic actions result primarily from mitochondrial inner membran...
Source: FEBS Letters - December 6, 2023 Category: Biochemistry Authors: Francesco De Leonardis, Amer Ahmed, Angelo Vozza, Loredana Capobianco, Christopher L. Riley, Simona Nicole Barile, Daria Di Molfetta, Stefano Tiziani, John DiGiovanni, Luigi Palmieri, Vincenza Dolce, Giuseppe Fiermonte Tags: Research Letter Source Type: research