Weibel-Palade bodies (WPBs) are secretory granules that contain von Willebrand factor and P-selectin, molecules that regulate hemostasis and inflammation, respectively. The presence of CD63/LAMP3 in the limiting membrane of WPBs has led to their classification as lysosome-related organelles. Many lysosome-related organelles contain intraluminal vesicles (ILVs) enriched in CD63 that are secreted into the extracellular environment during cell activation to mediate intercellular communication. To date, there are no reports that WPBs contain or release ILVs. By light microscopy and live-cell imaging, we show that CD63 is enriched in microdomains within WPBs. Extracellular antibody recycling studies showed that CD63 in WPB microdomains can originate from the plasma membrane. By cryo-electron tomography of frozen-hydrated endothelial cells, we identify internal vesicles as novel structural features of the WPB lumen. By live-cell fluorescence microscopy, we directly observe the exocytotic release of EGFP-CD63 ILVs as discrete particles from individual WPBs. WPB exocytosis provides a novel route for release of ILVs during endothelial cell stimulation.
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http://dx.doi.org/10.1182/blood-2018-09-874552 | DOI Listing |
Biochim Biophys Acta Biomembr
December 2024
Department of Medical BioSciences, Radboud University Medical Center, Radboud Institute for Medical Innovation, Nijmegen, the Netherlands. Electronic address:
Tetraspanins are four-transmembrane proteins that play fundamental roles in the immune system by enabling processes like migration, proliferation, signaling and protein trafficking. While the importance of cell surface tetraspanins has been established, the function of intracellular tetraspanins is less well understood. Here, we investigated the role of tetraspanin 3 (Tspan3) in lymphocytes.
View Article and Find Full Text PDFJ Extracell Biol
November 2024
Cell Metabolism Lab (GA-08), Department of Developmental Biology and Genetics (DBG) Indian Institute of Science (IISc) Bengaluru India.
Multivesicular bodies (MVBs) are vesicles of endosomal origin containing intraluminal vesicles, which upon fusion with plasma membrane, secrete exosomes. They play a significant role in the physiology and pathology of type-2 diabetes (T2D) due to disrupted intercellular communication. The role of MVBs and their influence on insulin secretory granules (ISGs) of β-cells or their characterization is yet to be uncovered.
View Article and Find Full Text PDFInt J Nanomedicine
November 2024
Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310053, People's Republic of China.
Background: Infected bone defects pose a challenging clinical issue due to an imbalance of osteoclasts (OC) and osteoblasts (OB). Exosomes are crucial for intercellular signaling of OC and OB in bone repair. Icariin, has been shown to regulate the balance between OC and OB.
View Article and Find Full Text PDFElife
November 2024
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
The spatiotemporal transition of small GTPase Rab5 to Rab7 is crucial for early-to-late endosome maturation, yet the precise mechanism governing Rab5-to-Rab7 switching remains elusive. USP8, a ubiquitin-specific protease, plays a prominent role in the endosomal sorting of a wide range of transmembrane receptors and is a promising target in cancer therapy. Here, we identified that USP8 is recruited to Rab5-positive carriers by Rabex5, a guanine nucleotide exchange factor (GEF) for Rab5.
View Article and Find Full Text PDFStem Cell Res Ther
November 2024
Department of Plastic and Aesthetic (Burn) Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Background: Exosomes (Exos) from adipose-derived stem cells (ADSCs) have a high inclusion content and low immunogenicity, which helps to control inflammation and accelerate the healing of wounds. Unfortunately, the yield of exosomes is poor, which raises the expense and lengthens the treatment period in addition to impairing exosomes' therapeutic impact. Thus, one of the key problems that needs to be resolved in the current exosome study is increasing the exosome yield.
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