Compartment-Specific Lysosomal Heterogeneity in Microglia Is Regulated by Adaptor Protein Complex-4
- 1University of Illinois at Chicago
Abstract
Microglia rely on lysosomes to clear phagocytosed material and orchestrate immune responses, but the mechanisms governing glial lysosome diversity and function remain largely undefined. Using high-resolution, high-throughput 3D imaging of mouse brain tissue, we find that glial lysosomes are heterogeneous in size and protease content depending on subcellular location. CD68+ and LAMP1+ vesicles were more numerous in glial processes than cell bodies; process LAMP1+ vesicles carried less protease than cell-body vesicles, but CD68+ protease content did not differ between compartments, revealing at least two lysosomal subpopulations within processes. Loss of Adaptor Protein complex 4 (AP-4) selectively remodels this landscape: it increases CD68+ vesicle number and CD68 enrichment, particularly in processes, without changing protease content, and disrupts the normal cell-body-versus-process pattern in protease- and CD68-enrichment. AP-4 loss also lowers protease content in cell-body LAMP1+ vesicles, mirroring a neuronal phenotype. These results provide the first evidence of glial lysosome heterogeneity and implicate AP-4 in shaping microglial lysosome composition and inflammatory function.
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BibTeX
@misc{somodji2026compartmentspecific,
title = {{Compartment-Specific Lysosomal Heterogeneity in Microglia Is Regulated by Adaptor Protein Complex-4}},
author = {E. Somodji and S. Gowrishankar},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.17.752408},
url = {https://www.biorxiv.org/content/10.64898/2026.09.17.752408v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Compartment-Specific Lysosomal Heterogeneity in Microglia Is Regulated by Adaptor Protein Complex-4
AU - E. Somodji
AU - S. Gowrishankar
PY - 2026
DA - 2026/09/17
PB - bioRxiv
DO - 10.64898/2026.09.17.752408
UR - https://www.biorxiv.org/content/10.64898/2026.09.17.752408v1
AB - Microglia rely on lysosomes to clear phagocytosed material and orchestrate immune responses, but the mechanisms governing glial lysosome diversity and function remain largely undefined. Using high-resolution, high-throughput 3D imaging of mouse brain tissue, we find that glial lysosomes are heterogeneous in size and protease content depending on subcellular location. CD68+ and LAMP1+ vesicles were more numerous in glial processes than cell bodies; process LAMP1+ vesicles carried less protease than cell-body vesicles, but CD68+ protease content did not differ between compartments, revealing at least two lysosomal subpopulations within processes. Loss of Adaptor Protein complex 4 (AP-4) selectively remodels this landscape: it increases CD68+ vesicle number and CD68 enrichment, particularly in processes, without changing protease content, and disrupts the normal cell-body-versus-process pattern in protease- and CD68-enrichment. AP-4 loss also lowers protease content in cell-body LAMP1+ vesicles, mirroring a neuronal phenotype. These results provide the first evidence of glial lysosome heterogeneity and implicate AP-4 in shaping microglial lysosome composition and inflammatory function.
ER -