title: Population distribution analyses reveal a hierarchy of molecular players underlying parallel endocytic pathways.
abstract: Single-cell-resolved measurements reveal heterogeneous distributions of clathrin-dependent (CD) and -independent (CLIC/GEEC: CG) endocytic activity in Drosophila cell populations. dsRNA-mediated knockdown of core versus peripheral endocytic machinery induces strong changes in the mean, or subtle changes in the shapes of these distributions, respectively. By quantifying these subtle shape changes for 27 single-cell features which report on endocytic activity and cell morphology, we organize 1072 Drosophila genes into a tree-like hierarchy. We find that tree nodes contain gene sets enriched in functional classes and protein complexes, providing a portrait of core and peripheral control of CD and CG endocytosis. For 470 genes we obtain additional features from separate assays and classify them into early- or late-acting genes of the endocytic pathways. Detailed analyses of specific genes at intermediate levels of the tree suggest that Vacuolar ATPase and lysosomal genes involved in vacuolar biogenesis play an evolutionarily conserved role in CG endocytosis.
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.
authors: Gagan D
authors: GD
authors: Gupta
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.
authors: Gautam
authors: G
authors: Dey
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.
authors: M G
authors: MG
authors: Swetha
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.
authors: Balaji
authors: B
authors: Ramalingam
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.
authors: Khader
authors: K
authors: Shameer
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.
authors: Joseph Jose
authors: JJ
authors: Thottacherry
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.
authors: Joseph Mathew
authors: JM
authors: Kalappurakkal
authors: The University of Queensland, Institute for Molecular Bioscience, Queensland, Australia.
authors: Mark T
authors: MT
authors: Howes
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.
authors: Ruma
authors: R
authors: Chandran
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.
authors: Anupam
authors: A
authors: Das
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.
authors: Sindhu
authors: S
authors: Menon
authors: The University of Queensland, Institute for Molecular Bioscience, Queensland, Australia.
authors: Robert G
authors: RG
authors: Parton
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.
authors: R
authors: R
authors: Sowdhamini
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.
authors: Mukund
authors: M
authors: Thattai
authors: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.
authors: Satyajit
authors: S
authors: Mayor
mesh_terms: D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000235:genetics / Q000502:physiology*; D005136:Eye Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006434:Hemocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D050765:Qa-SNARE Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism
chemical_list: D002966:Clathrin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D050765:Qa-SNARE Proteins; D034741:RNA, Small Interfering; C400361:car protein, Drosophila; C578392:syntaxin, Drosophila; D025262:Vacuolar Proton-Translocating ATPases