Membrane-bound organelles and membraneless organelles (MLOs) coordinate various biological processes within eukaryotic cells. Among these, stress granules (SGs) are significant cytoplasmic MLOs that form in response to cellular stress, exhibiting liquid-like properties alongside stable substructures. SGs interact with diverse organelles, thereby influencing cellular pathways that are critical in both health and disease contexts. This review discusses the interplay between SGs and organelles and explores the methodologies employed to analyze interactions between SGs and other MLOs. Furthermore, it highlights the pivotal roles SGs play in regulating cellular responses and the pathogenesis of amyotrophic lateral sclerosis. Gaining insights into these interactions is essential for deciphering the mechanisms underlying both physiological processes and pathological conditions.
Humans ; Stress Granules/pathology* ; Organelles/metabolism* ; Amyotrophic Lateral Sclerosis/pathology* ; Animals ; Stress, Physiological ; Cytoplasmic Granules/metabolism*

Stress granules (SGs) are cytoplasmic ribonucleoprotein assemblies formed under stress conditions and are related to various biological processes and human diseases. Previous studies have reported the regulatory role of some proteins and linear RNAs in SG assembly. However, the relationship between circular RNAs (circRNAs) and SGs has not been discovered. Here, we screened both linear RNAs and circRNAs in SGs using improved total RNA sequencing of purified SG cores in mammalian cells and identified circular transcripts specifically localized in SGs. circRNAs with higher SG-related RNA-binding protein (RBP) binding abilities are more likely to be enriched in SGs. Furthermore, some SG-enriched circRNAs are differentially expressed in hepatocellular carcinoma (HCC) and adjacent tissues. These results suggest the regulatory role of circRNAs in SG formation and provide insights into the biological function of circRNAs and SGs in HCC.
Animals ; Humans ; RNA, Circular/metabolism* ; Carcinoma, Hepatocellular/metabolism* ; Stress Granules ; Cytoplasmic Granules/metabolism* ; Liver Neoplasms/metabolism* ; RNA/metabolism* ; Stress, Physiological/genetics* ; Mammals/genetics*

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
Amyloidogenic Proteins/metabolism* ; Amyotrophic Lateral Sclerosis/genetics* ; Animals ; COVID-19 ; Cytoplasmic Granules/metabolism* ; Mammals ; SARS-CoV-2 ; Stress Granules

T-cell internal antigen-1 (TIA-1) has roles in regulating alternative pre-mRNA splicing, mRNA translation, and stress granule (SG) formation in human cells. As an evolutionarily conserved response to environmental stress, SGs have been reported in various species. However, SG formation in chicken cells and the role of chicken TIA-1 (cTIA-1) in SG assembly has not been elucidated. In the present study, we cloned cTIA-1 and showed that it facilitates the assembly of canonical SGs in both human and chicken cells. Overexpression of the chicken prion-related domain (cPRD) of cTIA-1 that bore an N-terminal green fluorescent protein (GFP) tag (pntGFP-cPRD) or Flag tag (pFlag-cPRD) induced the production of typical SGs. However, C-terminal GFP-tagged cPRD induced notably large cytoplasmic granules that were devoid of endogenous G3BP1 and remained stable when exposed to cycloheximide, indicating that these were not typical SGs, and that the pntGFP tag influences cPRD localization. Finally, endogenous cTIA-1 was recruited to SGs in chicken cells and tissues under environmental stress. Taken together, our study provide evidence that cTIA-1 has a role in canonical SG formation in chicken cells and tissues. Our results also indicate that cPRD is necessary for SG aggregation.
Chickens ; Clone Cells ; Cycloheximide ; Cytoplasmic Granules ; Humans ; Protein Biosynthesis ; RNA Precursors ; RNA-Binding Proteins ; T-Lymphocytes

Cytoplasmic Granules ; metabolism ; Drug Evaluation, Preclinical ; methods ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; HeLa Cells ; Humans

Mastocytosis is characterized by an accumulation of mast cells in various organs, most frequently in the skin. A solitary mastocytoma is a clinical variant of cutaneous mastocytosis. It is defined as a localized collection of mast cells in the skin without evidence of extracutaneous organ involvement. Here we report on a 2-year-old female patient presenting with Solitary erythematous bulla on her lower back. The patient had a history of spinal tap on the lower back for evaluation of meningitis at 5 months of age, which resulted in trauma at the site. Histopathology showed mast cells infiltrating the papillary and reticular dermis and metachromatic purple cytoplasmic granules seen with Giemsa staining. As a result, the patient was diagnosed with a solitary bullous mastocytoma and administered antihistamine. The patient showed complete remission at 3 months. Herein, we report a rare case of solitary bullous mastocytoma occurring at a trauma site.
Azure Stains ; Child, Preschool ; Cytoplasmic Granules ; Dermis ; Female ; Humans ; Mast Cells ; Mastocytoma* ; Mastocytosis ; Mastocytosis, Cutaneous ; Meningitis ; Skin ; Spinal Puncture*

Aged ; Cytoplasm ; Cytoplasmic Granules ; Female ; Humans ; Multiple Myeloma ; pathology ; Plasma Cells ; pathology

Myeloid sarcoma is a rare extramedullary myeloid tumor, which is frequently misdiagnosed when no evidence of leukemia is initially observed. Here, we report on a peculiar case of a 49-year-old man afflicted with multiple masses in the jejunum, the superior mesentery, and the serosa of the transverse colon, without leukemic manifestation. The tumor was composed of undifferentiated small round cells containing eosinophilic cytoplasm, which were negative for myeloperoxidase, nonspecific esterase, lysozyme, terminal deoxynucleotidyl transferase, leukocyte common antigen, CD3, CD4, CD15, CD20, CD30, CD43, CD56, CD68/PG-M1, CD79a, human melanoma black-45, c-kit, and CD34 with positivity only for CD68/KP1, CD99, and vimentin. Under electron microscopy, those cells had abundant membrane-bound cytoplasmic granules that measured 200 to 300 nm in diameter, which were consistent with granulocytic azurophilic granules. The tumor was finally diagnosed as a myeloid sarcoma. The presence of non-leukemic myeloid sarcomas showing immunonegativity for conventional myeloid-leukemic markers necessitated a diagnosis by ultrastructural observation.
Antigens, CD45 ; Carboxylesterase ; Colon, Transverse ; Cytoplasm ; Cytoplasmic Granules ; DNA Nucleotidylexotransferase ; Eosinophils ; Humans ; Intestinal Obstruction ; Jejunum ; Leukemia ; Melanoma ; Mesentery ; Microscopy, Electron ; Muramidase ; Peroxidase ; Sarcoma, Myeloid ; Serous Membrane ; Vimentin

Eosinophils are one of the polymorphonuclear granulocytes derived from bone marrow stem cells, and they contain many small cytoplasmic granules that stain bright red with eosin or brick-red with Romanowsky staining. Eosinophilic infiltration is also present in various human central nervous system (CNS) diseases such as parasitic infection, transverse myelitis, vasculitis, Langerhans cell histiocytosis, glioblastoma and etc... Due to the morphologic and functional characteristics, the presence of eosinophils in certain lesions may provide useful diagnostic clues in the right clinical setting. Consideration of this finding may facilitate the diagnosis of CNS pathologic lesions, especially in a small specimen such as a stereotactic biopsy.
Biopsy ; Bone Marrow ; Central Nervous System ; Cytoplasmic Granules ; Eosine Yellowish-(YS) ; Eosinophils ; Glioblastoma ; Granulocytes ; Histiocytosis, Langerhans-Cell ; Humans ; Myelitis, Transverse ; Stem Cells ; Vasculitis

Although bulk endocytosis has been found in a number of neuronal and endocrine cells, the molecular mechanism and physiological function of bulk endocytosis remain elusive. In pancreatic beta cells, we have observed bulk-like endocytosis evoked both by flash photolysis and trains of depolarization. Bulk-like endocytosis is a clathrin-independent process that is facilitated by enhanced extracellular Ca(2+) entry and suppressed by the inhibition of dynamin function. Moreover, defects in bulk-like endocytosis are accompanied by hyperinsulinemia in primary beta cells dissociated from diabetic KKAy mice, which suggests that bulk-like endocytosis plays an important role in maintaining the exo-endocytosis balance and beta cell secretory capability.
Animals ; Calcium ; metabolism ; Cytoplasmic Granules ; metabolism ; Diabetes Mellitus ; metabolism ; pathology ; Disease Models, Animal ; Dynamins ; metabolism ; Electric Capacitance ; Endocytosis ; physiology ; Insulin ; metabolism ; Insulin-Secreting Cells ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Patch-Clamp Techniques ; Photolysis ; Primary Cell Culture