Progranulin-derived granulin E and lysosome membrane protein CD68 interact to reciprocally regulate their protein homeostasis

• DOI: 10.1016/j.jbc.2022.102348
• Publication Date: 2022-08-04T05:35:36Z
• Authors: Mariela Nunez Santos; Daniel H. Paushter; Tingting Zhang; Xiaochun Wu; Tuancheng Feng; Jiaoying Lou; Huan Du; Stephanie M. Becker; Robert Fragoza; Haiyuan Yu; Fenghua Hu
• Keywords: CD68; Membrane glycoproteins

Progranulin (PGRN) is a glycoprotein implicated in several neurodegenerative diseases. It highly expressed microglia and macrophages can be secreted or delivered to the lysosome compartment. PGRN comprises 7.5 granulin repeats processed into individual peptides within lysosome, but functions of these are largely unknown. Here, we identify CD68, membrane protein mainly hematopoietic cells, as binding partner PGRN-derived E. Deletion analysis CD68 showed that this interaction mediated by mucin-proline-rich domain CD68. While deficiency does not affect lysosomal localization PGRN, it results specific decrease levels E no other peptides. On hand, its derivative peptides, leads significant shift molecular weight without altering cell. Our support reciprocally regulate each other's homeostasis.