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2015 ; 33
(2
): 163-75
Nephropedia Template TP
gab.com Text
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English Wikipedia
CALM regulates clathrin-coated vesicle size and maturation by directly sensing
and driving membrane curvature
#MMPMID25898166
Miller SE
; Mathiasen S
; Bright NA
; Pierre F
; Kelly BT
; Kladt N
; Schauss A
; Merrifield CJ
; Stamou D
; Höning S
; Owen DJ
Dev Cell
2015[Apr]; 33
(2
): 163-75
PMID25898166
show ga
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.