Endocytosis and cell fate determination

Notch pathway

Notch signaling pathway

nervous system: selection of a single neuroblast
(lateral inhibition)

Notch transmembrane protein

DSL familyDelta, Serrate, Lag-2

Kuzbaniancleave Notch ECD

Presenilincleave Notch ICD

Cleavage of Notch
Kuzbaniancleave Notch ECD

Presenilincleave Notch ICD

Dissociated NotchECD colocalizes with Delta in

control retinas discs.
wt
red

green

vesicles

green

surface

shi

Ts320C

red

Shi=dynamin

vesicles

Development, 127, 1373, 2000

The endocytosis of Notch ligands

is required for notch activation

Cell 124,897

Ligand-engaged and unliganded Notch

Cell 124,897,2006

Creation of asymmetry in pIIa and pIIb cells

1. Notch endocytosis
(Numb and -adaptin)
2. Sanpodo (required for Notch
signaling) endocytosis
3. Delta internalization to
Rab11 (+) recycling endosome
and recycle to plasma membrane

Rab11 based mechanism is suppressed

Cell 124,897,2006