SCIENCE@home

Deficiency of BLOS1 moderately impairs the biogenesis of platelet dense granules

Yefeng Yuan,Wei Li

Published 2025 in Platelets

ABSTRACT

ABSTRACT Defects in platelet secretion contribute to hemorrhagic disorders and coagulopathies, primarily link to the biogenesis of lysosome-related organelles (LROs), namely alpha granules (AGs) and dense granules (DGs). While deficiencies in the biogenesis of lysosome-related organelles complex-1 (BLOC-1) are known to impair DG formation and platelet function, the distinct roles of individual BLOC-1 subunits remain unresolved. Here, we investigated BLOS1, a shared subunit of BLOC-1 and BLOC-1-related complex (BORC) encoded by BLOC1S1. Through comparative analysis of platelet-specific Bloc1s1-conditional knockout (Bloc1s1-cKO) mice and sdy mice (deficiency in BLOC-1 subunit dysbindin), we found that Bloc1s1-cKO platelets exhibited a 50% reduction in DG content compared to sdy mice, indicating BLOS1 deficiency causes moderate DG biogenesis defects. Consistently, agonist-induced DG secretion in Bloc1s1-cKO mice was moderately impaired relative to the severe defects in sdy mice. Distinct steady-state levels of granule proteins were observed between the two mutants. These findings suggest that dysbindin (only in BLOC-1) and BLOS1 (a shared BLOC-1 and BORC subunit) regulate LRO biogenesis and function in a different manner. Plain Language Summary What is the context? Platelets are critical for clotting and preventing excessive bleeding. They rely on the storage pools called dense granules (DGs) to release substances that promote clotting. Defects in DG formation are linked to bleeding disorders. BLOS1 and dysbindin are subunits of BLOC-1, which functions in intracellular trafficking of cargoes. Unlike dysbindin, BLOS1 also belongs to another BORC complex, suggesting it may have unique roles in cellular processes. What is new? This study compared mice lacking BLOS1 only in platelets (Bloc1s1-cKO) with mice conventionally lacking dysbindin (sdy). Bloc1s1-cKO mice had about 50% fewer DGs than healthy mice, while sdy mice had almost no DGs. BLOS1-deficient platelets released fewer DG contents (e.g. ADP and serotonin) with impaired clotting, but less severe than in sdy mice. The findings suggest BLOS1 and dysbindin have different roles in DG biogenesis. This work highlights that each subunit of a complex may form a specific connectome governing different physiological functions. This may be important to understand the complexity of phenotypes in clinical practice.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-48 of 48 references · Page 1 of 1

CITED BY

  • No citing papers are available for this paper.

Showing 0-0 of 0 citing papers · Page 1 of 1