Key roles of Arf small G proteins and biosynthetic trafficking for animal development

Abstract

Although biosynthetic trafficking can function constitutively, it also functions specifically for certain developmental processes. These processes require either a large increase to biosynthesis or the biosynthesis and targeted trafficking of specific players. We review the conserved molecular mechanisms that direct biosynthetic trafficking, and discuss how their genetic disruption affects animal development. Specifically, we consider Arf small G proteins, such as Arf1 and Sar1, and their coat effectors, COPI and COPII, and how these proteins promote biosynthetic trafficking for cleavage of the Drosophila embryo, the growth of neuronal dendrites and synapses, extracellular matrix secretion for bone development, lumen development in epithelial tubes, notochord and neural tube development, and ciliogenesis. Specific need for the biosynthetic trafficking system is also evident from conserved CrebA/Creb3-like transcription factors increasing the expression of secretory machinery during several of these developmental processes. Moreover, dysfunctional trafficking leads to a range of developmental syndromes.

Identification of Genes Required for Apical Protein Trafficking inDrosophilaPhotoreceptor Cells

“…Candidates to consider are Arf1, Arf4, and Arl1. Arf1 (Arf79F in Drosophila ), is important in regulating traffic at the Golgi apparatus (Rodrigues and Harris 2017). In sensory neurons, Sec71 activates Arf1, and the Golgi apparatus is disrupted in Arf1 mutant cells (Wang et al , 2017).…”

Dominantly acting variants in ARF3 have disruptive consequences on Golgi integrity and cause microcephaly recapitulated in zebrafish

“…The small GTPases of the ARF family are highly conserved across eukaryotes, occupy different subcellular compartments involved in ER-GA network, and have both redundant and distinct functions 11 . These proteins control key molecular and cellular processes, including targeted intracellular trafficking of signaling proteins, cell migration and division, lipid metabolism, and signaling, which are important during animal development 1,32,33 . The intracellular localization and activity of ARF3 at the trans-Golgi, where it promotes recruitment of coat complexes and vesicle formation, is tightly regulated via a conformational switch controlled by reversible GDP-to-GTP binding 12,16 .…”

In vivo Functional Genomics for Undiagnosed Patients: The Impact of Small GTPases Signaling Dysregulation at Pan-Embryo Developmental Scale

“…In cancer, the aberrant activity of these proteins can modulate negatively various tumorigenic steps (including metastasis), where they can work both as oncogenes and tumor suppressors (a role recently reviewed by Casalou et al, 2020 andGopal Krishnan et al, 2020). Besides the cases discussed below, the role of ARF and ARF-related proteins in animal development was recently reviewed in pathological contexts by Rodrigues and Harris (2019).…”

“…Acting on shaping developmental signals strength and distribution and regulating cell behavior, ARF and RABcontrolled biosynthetic trafficking globally modulates morphogens' distribution and function in developmental programs. The regulated process of polarized vesicular transport of morphogenes guarantees coordinated cell-cell signals and movements during development, ultimately leading to cell specification and organogenesis (Eaton and Martin-Belmonte, 2014;Wada et al, 2016;Rodrigues and Harris, 2019). Indeed, an aberrant function of ER and GA enzymes impairs proteins' modification, with a deleterious impact on Wnt, Notch, and FGF signaling, as shown in insects and rodents (Biechele et al, 2011;Fernandez-Valdivia et al, 2011;Shimokawa et al, 2011).…”