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Defects in early secretory pathway transport machinery components and neurodevelopmental disorders

  • Bor Luen Tang EMAIL logo
Published/Copyright: March 30, 2021
Become an author with De Gruyter Brill

Abstract

The early secretory pathway, provisionally comprising of vesicular traffic between the endoplasmic reticulum (ER) and the Golgi apparatus, occurs constitutively in mammalian cells. Critical for a constant supply of secretory and plasma membrane (PM) materials, the pathway is presumably essential for general cellular function and survival. Neurons exhibit a high intensity in membrane dynamics and protein/lipid trafficking, with differential and polarized trafficking towards the somatodendritic and axonal PM domains. Mutations in genes encoding early secretory pathway membrane trafficking machinery components are known to result in neurodevelopmental or neurological disorders with disease manifestation in early life. Here, such rare disorders associated with autosomal recessive mutations in coat proteins, membrane tethering complexes and membrane fusion machineries responsible for trafficking in the early secretory pathway are summarily discussed. These mutations affected genes encoding subunits of coat protein complex I and II, subunits of transport protein particle (TRAPP) complexes, members of the YIP1 domain family (YIPF) and a SNAP receptor (SNARE) family member. Why the ubiquitously present and constitutively acting early secretory pathway machinery components could specifically affect neurodevelopment is addressed, with the plausible underlying disease etiologies and neuropathological mechanisms resulting from these mutations explored.


Corresponding author: Bor Luen Tang, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore, E-mail:

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Received: 2021-02-08
Accepted: 2021-03-12
Published Online: 2021-03-30
Published in Print: 2021-12-20

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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