Defects in early secretory pathway transport machinery components and neurodevelopmental disorders
Affiliation:
1. Department of Biochemistry , Yong Loo Lin School of Medicine, National University of Singapore , 8 Medical Drive , Singapore 117597 , Singapore
Abstract
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.
Publisher
Walter de Gruyter GmbH
Subject
General Neuroscience
Reference199 articles.
1. Abbasi, A.A., Blaesius, K., Hu, H., Latif, Z., Picker-Minh, S., Khan, M.N., Farooq, S., Khan, M.A., and Kaindl, A.M. (2017). Identification of a novel homozygous TRAPPC9 gene mutation causing non-syndromic intellectual disability, speech disorder, and secondary microcephaly. Am. J. Med. Genet. B Neuropsychiatr. Genet. 174: 839–845. https://doi.org/10.1002/ajmg.b.32602. 2. Abdel-Salam, G.M.H., Schaffer, A.E., Zaki, M.S., Dixon-Salazar, T., Mostafa, I.S., Afifi, H.H., and Gleeson, J.G. (2012). A homozygous IER3IP1 mutation causes microcephaly with simplified gyral pattern, epilepsy, and permanent neonatal diabetes syndrome (MEDS). Am. J. Med. Genet. 158: 2788–2796. 3. Al Awabdh, S., Miserey-Lenkei, S., Bouceba, T., Masson, J., Kano, F., Marinach-Patrice, C., Hamon, M., Emerit, M.B., and Darmon, M. (2012). A new vesicular scaffolding complex mediates the G-protein-coupled 5-HT1A receptor targeting to neuronal dendrites. J. Neurosci. 32: 14227–14241. https://doi.org/10.1523/jneurosci.6329-11.2012. 4. Al-Deri, N., Okur, V., Ahimaz, P., Milev, M., Valivullah, Z., Hagen, J., Sheng, Y., Chung, W., Sacher, M., and Ganapathi, M. (2021). A novel homozygous variant in TRAPPC2L results in a neurodevelopmental disorder and disrupts TRAPP complex function. J. Med. Genet. 58: 592–601. https://doi.org/10.1136/jmedgenet-2020-107016. 5. AlMuhaizea, M., AlMass, R., AlHargan, A., AlBader, A., Medico Salsench, E., Howaidi, J., Ihinger, J., Karachunski, P., Begtrup, A., Segura Castell, M., et al.. (2020). Truncating mutations in YIF1B cause a progressive encephalopathy with various degrees of mixed movement disorder, microcephaly, and epilepsy. Acta Neuropathol. 139: 791–794. https://doi.org/10.1007/s00401-020-02128-8.
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|