Lis-1 (Drosophila melanogaster, Q7KNS3) — review notes

2026-09-27 — initial review (claude-code)

Sources: UniProt Q7KNS3, cached GOA-cited publications (full text for PMID:16107559, 22764052, 23918939,
21041636, 18946501, 22808215, 28837701, 26265702, 25694447, 18758451, 21943192; abstract-only for the rest).
Deep research (falcon) was not yet available when this review was written.

Core biology

• Lis1 physically associates with dynein and dynactin in fly extracts PMID:16107559.
• Lis1 recruits dynein-dynactin to mRNA cargo and promotes dynein-dynactin association PMID:23918939.
• Required for dynein-dynactin recruitment to nuclear surface and spindle poles in male germ cells PMID:22764052.
• Nuclear migration: oocyte nucleus positioning, with genetic interactions with Glued and Dhc PMID:10993674; with BicD/Egl in oocyte determination PMID:10559989.
• Mitosis: centrosome separation, spindle assembly, poleward stripping of Rod from kinetochores PMID:16107559.
• Neurons: neuroblast proliferation, dendrite arborization, axonal transport PMID:11056531; retrograde transport of Neuroglian PMID:28837701 and Dscam restriction PMID:18946501.
• Fly Lis1 does not bind the fly PAF-AH alpha homolog PMID:10737922, so the PAF-AH regulatory-subunit role of human LIS1 is not supported in flies.
• Lineage-/tissue-specific: Lis1 binds and stabilises Mad in GSCs (co-IP in S2 cells) PMID:21041636.

Decisions

• MF: added NEW GO:0140659 cytoskeletal motor regulator activity (matches human PAFAH1B1 review and nucleokinesis module).
• protein binding (Mad) -> MODIFY to GO:0046332 SMAD binding.
• dynein complex / dynactin complex (part_of) -> MODIFY to GO:0005875 microtubule associated complex: LIS1 is a transient regulator, not a stoichiometric subunit; association captured by GO:0070840.
• Muscle cell cellular homeostasis (PMID:21256839): UNDECIDED; abstract-only and does not mention Lis1.
• Developmental processes (oogenesis, fusome, dendrite, border cell migration, GSC) kept as non-core.

2026-09-27 — Falcon deep research incorporated

• Read Lis-1-deep-research-falcon.md. It agrees with the review: Lis-1 is a non-catalytic, context-dependent dynein-dynactin regulator/assembly factor; fly phenotypes (oogenesis, neuroblast mitosis, spermatogenesis, mRNA transport, border cells) are downstream of dynein regulation.
• Its fly-specific claims map onto already-cached primary papers (PMID:16107559, 22764052, 23918939, 22808215, 10498683/10559989); mechanistic 2024 claims (Singh et al. Science 2024; Kusakci et al. 2024) are non-fly and were not cached or cited as primary evidence.
• Added the report as retrieval support for the NEW GO:0140659 row and the core function (regulator parent term rather than inhibitor/activator). No actions changed; no new PMIDs.