cellular physiology - endoplasmic reticulum

Introduction

the cells of all animals, plants and fungi contain specialised criss-crossing of tubes and membranes called endoplasmic reticulum (ER)
endoplasmic reticulum is essentially a factory in which proteins, lipids and hormones are manufactured, folded into their three-dimensional structure and modified
ER also controls calcium concentrations in the cell and forms the basis for the cellular transport system, feeds misfolded proteins to intracellular disposal and renders toxins that have entered the cell harmless
ER within a cell is constantly being remodeled via a process of ER-phagy (self-digestion which degrades faulty or unneeded ER)
- ER-phagy is driven by the protein ubiquitin which:
  - changes the shape of part of the FAM134B protein and causes the FAM134B clusters to become more stable and the ER to bulge out more at these sites. The stronger membrane curvature then leads to further stabilization of the clusters and, moreover, attracts additional membrane curvature proteins. So the effect of ubiquitin is self-reinforcing. ¹⁾
  - also effects the membrane curvature protein called ARL6IP1 which is also part of the ER-phagy processes

mutations in the FAM134B gene cause a very rare hereditary sensory and autonomic neuropathy (HSAN)
mutations in ARL6IP1 gene cause a similar neurodegenerative disorder which combines sensory defects with spasticity in the legs
in mice without ARL6IP1 protein, misfolded proteins or protein clumps are no longer disposed and accumulate within the cell which particularly affects neurons as they do not renew as fast as other cells
ER-phagy pathology thus may be an important mechanism of a range of neurodegenerative diseases

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