Agent-Based Model Derived from module 7 elements · 6 transitions

Agent-based model of retromer (VPS35/VPS26A/VPS29) and SORL1 endosome-to-TGN retrograde retrieval vs. RAB7A/CTSD lysosomal degradation

Simulates 100 discrete SORL1/sorting-receptor cargo agents traversing the seven stages of endocytic internalization and retrograde endosome-to-TGN retrieval under uniform uncalibrated default transition rates (base_rate = 0.45, competing_inhibitor_factor = 0.25). Under wild-type baseline conditions, active retromer recruitment (retromer_csc_cargo_selection) attenuates ESCRT/RAB7A degradative progression (escrt_rab7_degradative_routing), retrieving 80% of internalized receptor-cargo complexes to the trans-Golgi network (rab9a_ap1_tgn_delivery) while only 20% undergoes lysosomal proteolysis (ctsd_lysosomal_proteolysis). Inactivating the retromer complex (modeling VPS35/VPS26A/VPS29 deficiency) abolishes TGN retrieval and diverts 100% of internalized receptors into RAB7A/CTSD lysosomal degradation — while simultaneous RAB7A inhibition rescues cargo from lysosomal proteolysis, reproducing the genetic suppression of retromer loss by Rab7 reduction (PMID:32286230).

Module: Retromer (VPS35/VPS26A/VPS29) and SORL1 endosome-to-TGN retrograde sorting — clathrin/AP-2/DNM2 internalization, V-ATPase acidification, retromer cargo selection, and RAB9A/AP-1 TGN delivery vs. ESCRT/RAB7A/CTSD lysosomal proteolysis Source YAML: modules/retromer_endosome_to_tgn_retrieval.yaml

Compartment Trafficking & Discrete Cargo Routing

t = 24 / 24

Cargo Occupancy Trajectory (t = 0 .. 24)

Derived Transition Rules & Effective Flux Rates

From Stage To Stage Predicate Modulators / Competing Branches Effective Rate