Endoplasmic reticulum and Golgi stress in microcephaly

Authors:

Sandrine Passemard1,2, Franck Perez3, Pierre Gressens1,4 and Vincent El Ghouzzi1
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Affiliations:

1 Université de Paris, NeuroDiderot, Inserm, F-75019 Paris, France.

2 Service de Génétique Clinique, AP-HP, Hôpital Robert Debré, F-75019 Paris, France.

3 Institut Curie, PSL Research University, CNRS, UMR144, Paris, France

4 Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King’s College London, King’s Health Partners, St. Thomas’Hospital, London, United Kingdom.

Keywords: 

Golgi apparatus, endoplasmic reticulum, stress, UPR, corticogenesis, primary microcephaly, golgipathies.

Abbreviatons:

aRGC – apical radial glial cell,

BFA – brefeldin A,

bRGC – basal radial glial cell,

CDG - Congenital Disorders of Glycosylation,

CNS – central nervous system,

DDR – DNA damage repair,

DSB – double-strand break,

ER – endoplasmic reticulum,

ERAD – ER-associated degradation,

GA – Golgi apparatus,

GASE – Golgi apparatus stress response element,

GCA – golgicide A,

ID – intellectual disability,

IP – intermediate progenitor,

KEOPS – Kinase, Endopeptidase and Other Protein of small Size,

MON – monensin,

OFC – occipito-frontal circumference,

PM – primary microcephaly,

TGN – trans-Golgi network,

TRAPP – transport protein particle,

UPR – unfolded protein response,

ZIKV – ZIKA virus.

Corresponding Author(s):

Vincent El Ghouzzi, Inserm U1141, Hôpital Robert-Debré, 48 Boulevard Sérurier, F-75019, Paris, France; Phone: +331 40031973; Fax: +331 40031995; vincent.elghouzzi@inserm.fr Pierre Gressens, Inserm U1141, Hôpital Robert-Debré, 48 Boulevard Sérurier, F-75019, Paris, France; Phone: +331 40031901; Fax: +331 40031995; pierre.gressens@inserm.fr

Conflict of interest statement:

The authors declare no conflict of interest.

Please cite this article as:

Sandrine Passemard, Franck Perez, Pierre Gressens and Vincent El Ghouzzi (2019). Endoplasmic reticulum and golgi stress in microcephaly. Cell Stress 3(12): 369-384. doi: 10.15698/cst2019.12.206

© 2019 Passemard et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.

Abstract:

Microcephaly is a neurodevelopmental condition characterized by a small brain size associated with intellectual deficiency in most cases and is one of the most frequent clinical sign encountered in neurodevelopmental disorders. It can result from a wide range of environmental insults occurring during pregnancy or postnatally, as well as from various genetic causes and represents a highly heterogeneous condition. However, several lines of evidence highlight a compromised mode of division of the cortical precursor cells during neurogenesis, affecting neural commitment or survival as one of the common mechanisms leading to a limited production of neurons and associated with the most severe forms of congenital microcephaly. In this context, the emergence of the endoplasmic reticulum (ER) and the Golgi apparatus as key guardians of cellular homeostasis, especially through the regulation of proteostasis, has raised the hypothesis that pathological ER and/or Golgi stress could contribute significantly to cortical impairments eliciting microcephaly. In this review, we discuss recent findings implicating ER and Golgi stress responses in early brain development and provide an overview of microcephaly-associated genes involved in these pathways.