Lysosome-related organelles: driving post-Golgi compartments into specialisation

Abstract

Some cells harbour specialised lysosome-related organelles (LROs) that share features of late endosomes/lysosomes but are functionally, morphologically and/or compositionally distinct. Ubiquitous trafficking machineries cooperate with cell type specific cargoes to produce these organelles. Several genetic diseases are caused by dysfunctional LRO formation and/or motility. Many genes affected by these diseases have been recently identified, revealing new cellular components of the trafficking machinery. Current research reveals how the products of these genes cooperate to generate LROs and how these otherwise diverse organelles are related by the mechanisms through which they form.

Figure 1

LROs display different morphological features A: Melanosomes; B: Azurophilic granules; C: Cytolytic granules; D: MHC class II compartments (Here MIICs are immunogold labeled for MHC class II molecules); E: Weibel Palade Bodies

Figure 2

Comparative biogenesis of Melanosomes and Weibel-Palade Bodies This figure shows both the differences; origin in the TGN versus origin in the EE for these two organelles, and the similarities; continued receipt of content after initial formation (Tyrosinase versus CD63), and recruitment of Rabs. The overall image of a complex, multi-stage, gradual transformation of a post-Golgi (TGN versus EE) organelle into an LRO is similar for both. Gold coating, AP-1; Purple coating, AP-3; Grey coating on stage I melanosome, bilayered clathrin/Hrs coat. TGN, Trans-Golgi Network; EE, early endosome; MVB, multivesicular body/Late endosome; Tyr, Tyrosinase. Tyrp1, Tyrosinase Related Protein-1