|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
|
Fig. 7. Role of endocytosis and Lqf in sending DSL signals. (A,B) Examples of two
general models are shown, distinguished by whether the activation of Notch is
triggered by the early events of DSL endocytosis leading up to pinching off of
the coated vesicle (A), or is dependent on the recycling of DSL ligands (B).
To accommodate our results, we envisage that the first model (A) would require
Lqf (red) to be present, or active, in only a subset of coated pits or other
structures that provide a specialized micro-environment (dark gray) necessary
for productive interactions (pink scissors) between DSL ligands and Notch.
Cargo proteins, including DSL ligands (colored gold), that carry only
mono-Ubiquitin internalization signals would depend on Lqf to be recruited to
these specialized structures. Other adapters (blue) would internalize
mono-ubiquitinated DSL ligands via other structures that lack the necessary
environment for productive interactions to occur. In the second model (B), Lqf
and other adapters could co-exist in coated pits, with Lqf allowing
mono-ubiquitinated cargo to gain access, subsequently, to a recycling pathway.
Entry into this pathway would be essential for the conversion of nascent DSL
proteins into active ligands, for example by proteolytic processing (not
shown), which can then interact productively with Notch. In both models,
introduction of other internalization signals, such as the LDL receptor
signal, would allow DSL ligands to bypass the requirement for Lqf to enter the
required surface structures or recycling pathways. EE, early endosome; RE,
recycling endosome; LE/MVB, late endosome/multi-vesicular body; TGN,
trans-Golgi network.
|
