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Updated: Jan 8, 2026

In Situ Detection of Ribonucleoprotein Complex Assembly in the C. elegans Germline using Proximity Ligation Assay
Published on: May 5, 2020
COP9 signalosome and PRMT5 methylosome complexes are essential regulators of Lis1-dynein-based transport
Devanshi Gupta1, Subbareddy Maddika2
1Laboratory of Cell Death & Cell Survival, Centre for DNA Fingerprinting and Diagnostics (CDFD), Uppal, Hyderabad, India; Graduate Studies, Regional Centre for Biotechnology, Faridabad, India.
Abstract:
Cytoplasmic dynein drives minus-end-directed transport along microtubules, a process critically modulated by Lis1. Although Lis1 has been reported to both inhibit and activate dynein, the molecular basis for these opposing effects remains unclear. We identify the COP9 signalosome (CSN) and protein arginine methyltransferase 5 (PRMT5) complexes as key determinants of Lis1-dependent dynein regulation. Lis1 recruits CSN to dynein, promoting deneddylation and maintaining the motor in an inactive state, thus functioning as an off switch. Neddylation of dynein intermediate chain 1 (DIC1) at K42 is required for the assembly of active transport complexes. In contrast, PRMT5 methylates Lis1 at R238, switching Lis1 to a positive regulator. This modification displaces CSN from dynein, restores neddylation, and promotes motor activation and cargo transport. These findings reveal a dual regulatory axis in which Lis1 integrates CSN- and PRMT5-dependent cues to switch dynein between inactive and active states, providing a mechanistic basis for Lis1's contrasting roles in dynein control.
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