RGD Reference Report - CALM regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature. - Rat Genome Database

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CALM regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature.

Authors: Miller, Sharon E  Mathiasen, Signe  Bright, Nicholas A  Pierre, Fabienne  Kelly, Bernard T  Kladt, Nikolay  Schauss, Astrid  Merrifield, Christien J  Stamou, Dimitrios  Höning, Stefan  Owen, David J 
Citation: Miller SE, etal., Dev Cell. 2015 Apr 20;33(2):163-75. doi: 10.1016/j.devcel.2015.03.002.
RGD ID: 13210546
Pubmed: PMID:25898166   (View Abstract at PubMed)
PMCID: PMC4406947   (View Article at PubMed Central)
DOI: DOI:10.1016/j.devcel.2015.03.002   (Journal Full-text)

The size of endocytic clathrin-coated vesicles (CCVs) is remarkably uniform, suggesting that it is optimized to achieve the appropriate levels of cargo and lipid internalization. The three most abundant proteins in mammalian endocytic CCVs are clathrin and the two cargo-selecting, clathrin adaptors, CALM and AP2. Here we demonstrate that depletion of CALM causes a substantial increase in the ratio of "open" clathrin-coated pits (CCPs) to "necked"/"closed" CCVs and a doubling of CCP/CCV diameter, whereas AP2 depletion has opposite effects. Depletion of either adaptor, however, significantly inhibits endocytosis of transferrin and epidermal growth factor. The phenotypic effects of CALM depletion can be rescued by re-expression of wild-type CALM, but not with CALM that lacks a functional N-terminal, membrane-inserting, curvature-sensing/driving amphipathic helix, the existence and properties of which are demonstrated. CALM is thus a major factor in controlling CCV size and maturation and hence in determining the rates of endocytic cargo uptake.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
membrane located_inIMP 13210546PMID:25898166ARUK-UCL 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
phosphatidylinositol-4,5-bisphosphate binding enablesIMP 13210546PMID:25898166ARUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Picalm  (phosphatidylinositol binding clathrin assembly protein)


Additional Information