PMID- 18165318 OWN - NLM STAT- MEDLINE DCOM- 20080205 LR - 20211203 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 105 IP - 1 DP - 2008 Jan 8 TI - Clathrin light chains function in mannose phosphate receptor trafficking via regulation of actin assembly. PG - 168-73 LID - 10.1073/pnas.0707269105 [doi] AB - Clathrin-coated vesicles (CCVs) are major carriers for endocytic cargo and mediate important intracellular trafficking events at the trans-Golgi network (TGN) and endosomes. Whereas clathrin heavy chain provides the structural backbone of the clathrin coat, the role of clathrin light chains (CLCs) is poorly understood. We now demonstrate that CLCs are not required for clathrin-mediated endocytosis but are critical for clathrin-mediated trafficking between the TGN and the endosomal system. Specifically, CLC knockdown (KD) causes the cation-independent mannose-6 phosphate receptor (CI-MPR) to cluster near the TGN leading to a delay in processing of the lysosomal hydrolase cathepsin D. A recently identified binding partner for CLCs is huntingtin-interacting protein 1-related (HIP1R), which is required for productive interactions of CCVs with the actin cytoskeleton. CLC KD causes mislocalization of HIP1R and overassembly of actin, which accumulates in patches around the clustered CI-MPR. A dominant-negative CLC construct that disrupts HIP1R/CLC interactions causes similar alterations in CI-MPR trafficking and actin assembly. Thus, in mammalian cells CLCs function in intracellular membrane trafficking by acting as recruitment proteins for HIP1R, enabling HIP1R to regulate actin assembly on clathrin-coated structures. FAU - Poupon, Viviane AU - Poupon V AD - Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. FAU - Girard, Martine AU - Girard M FAU - Legendre-Guillemin, Valerie AU - Legendre-Guillemin V FAU - Thomas, Sebastien AU - Thomas S FAU - Bourbonniere, Lyne AU - Bourbonniere L FAU - Philie, Jacynthe AU - Philie J FAU - Bright, Nicholas A AU - Bright NA FAU - McPherson, Peter S AU - McPherson PS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071228 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Actins) RN - 0 (CD8 Antigens) RN - 0 (Clathrin Light Chains) RN - 0 (HAP1 protein, human) RN - 0 (Lectins, C-Type) RN - 0 (Mannose Receptor) RN - 0 (Mannose-Binding Lectins) RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Small Interfering) RN - 0 (Receptors, Cell Surface) RN - EC 3.4.23.5 (Cathepsin D) SB - IM MH - Actins/*chemistry MH - Animals MH - Biological Transport MH - CD8 Antigens/biosynthesis MH - COS Cells MH - Cathepsin D/chemistry/metabolism MH - Chlorocebus aethiops MH - Clathrin Light Chains/chemistry/*physiology MH - Endocytosis MH - Golgi Apparatus/metabolism MH - HeLa Cells MH - Humans MH - Lectins, C-Type/*metabolism MH - Mannose Receptor MH - Mannose-Binding Lectins/*metabolism MH - Models, Biological MH - Nerve Tissue Proteins/chemistry MH - RNA, Small Interfering/metabolism MH - Receptors, Cell Surface/*metabolism MH - trans-Golgi Network PMC - PMC2224180 COIS- The authors declare no conflict of interest. EDAT- 2008/01/01 09:00 MHDA- 2008/02/06 09:00 PMCR- 2008/07/08 CRDT- 2008/01/01 09:00 PHST- 2008/01/01 09:00 [pubmed] PHST- 2008/02/06 09:00 [medline] PHST- 2008/01/01 09:00 [entrez] PHST- 2008/07/08 00:00 [pmc-release] AID - 0707269105 [pii] AID - 8752 [pii] AID - 10.1073/pnas.0707269105 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):168-73. doi: 10.1073/pnas.0707269105. Epub 2007 Dec 28.