title: Cooperative interactions of LPPR family members in membrane localization and alteration of cellular morphology.
abstract: The lipid phosphate phosphatase-related proteins (LPPRs), also known as plasticity-related genes (PRGs), are classified as a new brain-enriched subclass of the lipid phosphate phosphatase (LPP) superfamily. They induce membrane protrusions, neurite outgrowth or dendritic spine formation in cell lines and primary neurons. However, the exact roles of LPPRs and the mechanisms underlying their effects are not certain. Here, we present the results of a large-scale proteome analysis to determine LPPR1-interacting proteins using co-immunoprecipitation coupled to mass spectrometry. We identified putative LPPR1-binding proteins involved in various biological processes. Most interestingly, we identified the interaction of LPPR1 with its family member LPPR3, LPPR4 and LPPR5. Their interactions were characterized by co-immunoprecipitation and colocalization analysis using confocal and super-resolution microscopy. Moreover, co-expressing two LPPR members mutually elevated their protein levels, facilitated their plasma membrane localization and resulted in an increased induction of membrane protrusions as well as the phosphorylation of S6 ribosomal protein. Taken together, we revealed a new functional cooperation between LPPR family members and discovered for the first time that LPPRs likely exert their function through forming complex with its family members.
authors.affiliation: Developmental Neurobiology Section, Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China yupanpan21@gmail.com geller@helix.nih.gov.
authors.forename: Panpan
authors.initials: P
authors.lastname: Yu
authors.affiliation: Developmental Neurobiology Section, Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA.
authors.forename: Chinyere
authors.initials: C
authors.lastname: Agbaegbu
authors.affiliation: Light Microscopy Core Facility, NHLBI, NIH, Bethesda, MD 20892, USA.
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Malide
authors.affiliation: Molecular Cell Biology Section, Cell Biology and Physiology Center, NHLBI, NIH, Bethesda, MD 20892, USA.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Developmental Neurobiology Section, Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Katagiri
authors.affiliation: Molecular Cell Biology Section, Cell Biology and Physiology Center, NHLBI, NIH, Bethesda, MD 20892, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Hammer
authors.affiliation: Developmental Neurobiology Section, Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA yupanpan21@gmail.com geller@helix.nih.gov.
authors.forename: Herbert M
authors.initials: HM
authors.lastname: Geller
mesh_terms: D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins; D010744:Phosphoric Monoester Hydrolases
keywords: Actin; Filopodia; Membrane protrusion; Protein-protein interaction