New lines of investigation may help us understand the precise mechanisms of RER sub-compartmentalization.
These differences suggest the existence of still further sub-compartmentalization along the length of the duct.
Changes in the rate of LAMP2A synthesis, its regulated degradation at the lysosomal membrane and its sub-compartmentalization to this organelle, all contribute to modulate CMA activity (Kaushik & Cuervo, 2012).
This suggests that P-bodies and age-associated protein deposits have different physicochemical properties, representing two distinct modes of cytosolic sub-compartmentalization (Hyman et al., 2014; Kroschwald et al., 2015).
Indeed, sufficiently large box sizes (low N) and sufficiently low diffusion coefficients show a discrepancy in the final position of the pinned wave between the retracting and the extending waves, illustrating how too slow diffusion combined with too coarse sub-compartmentalization leads to propagation failure.
Similar to the mouse, however, sub-compartmentalization of histone modifications was also detected in human embryos later in development between blastomeres at the morula stage and within the ICM and trophectoderm sub-populations at the blastocyst stage (Fig. 3B and Supplementary Material, Fig. S3b).
LAMP2A-mediated substrate binding and internalization are essential processes for CMA and, in fact, changes in LAMP2A levels, or changes in its sub-compartmentalization to the lysosomal membrane, all contribute to modulate CMA activity (Cuervo & Dice, 2000a, b; Massey et al, 2006a; Kaushik & Cuervo, 2012).
In particular, while mouse embryos first exhibited sub-compartmentalization of different histone modifications between blastomeres at the morula stage and cell sub-populations in blastocysts, differential histone modification expression was detected between blastomeres earlier in human embryos at the four- to eight-cell stage.
As Figure 3B and Supplementary Material, Figure S3a demonstrate, it was not until later in development (between the morula and blastocyst stages) that sub-compartmentalization of different epigenetic marks such as H3-S28P and H4-R3me2 was observed between blastomeres or cell populations within the same embryo (shown by white solid arrows).
In this light, it should be mentioned that the biggest challenge in the representation of the sub-cellular localization of eukaryotic metabolic pathways lies in acquiring the knowledge of sub-cellular compartmentalization of eukaryotic metabolic pathways.
It contains sub-cellular compartmentalization, co-localization via anchoring proteins, scaffolds, temporal and cell-type specific co-expression.
