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Emerging Roles for MFG-E8 in Synapse Elimination
Marisa G Aviani1, Fred Menard1,2
1Department of Biochemistry and Molecular Biology, I.K. Barber Faculty of Science, The University of British Columbia, Kelowna, British Columbia, Canada.
Abstract:
Synapse elimination is an essential process in the healthy nervous system and is dysregulated in many neuropathologies. Yet, the underlying molecular mechanisms and under what conditions they occur remain unclear. MFG-E8 is a secreted glycoprotein well known to act as an opsonin, tagging stressed and dying cells for engulfment by phagocytes. Opsonization of cells and debris by MFG-E8 for microglial phagocytosis in the CNS is well established, and its role in astrocytic phagocytosis, and trogocytosis-like engulfment of synapses is beginning to be explored. However, MFG-E8's function in other tissues is highly diverse, and evidence suggests that its role in the nervous system and on synapse elimination in particular may be more complex and varied than opsonization. In this review, we outline the documented direct and indirect effects of MFG-E8 on synapse elimination, while also proposing potential roles to be explored further, in particular, cytoskeletal reorganization of neurites and glia leading to synapse elimination by various mechanisms. Finally, we demonstrate the need for several open questions to be answered-chiefly, under what conditions might MFG-E8-mediated synapse elimination occur in favor of other mechanisms, and when might its activity be dysregulated, increasing unwanted synapse elimination and neurotoxicity?
Insights
Milk fat globule-epidermal growth factor 8 (MFG-E8) influences synapse elimination in the nervous system. This review explores MFG-E8
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Synapse elimination is crucial for nervous system development and function.
- Dysregulation of synapse elimination is implicated in neuropathologies.
- MFG-E8 is a secreted glycoprotein known for its role in phagocytosis.
Purpose of the Study:
- To review the known direct and indirect effects of MFG-E8 on synapse elimination.
- To propose potential novel mechanisms of MFG-E8 in synapse elimination, including cytoskeletal reorganization.
- To highlight open questions regarding the conditions and regulation of MFG-E8-mediated synapse elimination.
Main Methods:
- Literature review of existing studies on MFG-E8 and synapse elimination.
- Analysis of MFG-E8's established functions in phagocytosis and its potential roles in the nervous system.
- Synthesis of evidence to propose new hypotheses regarding MFG-E8's mechanisms.
Main Results:
- MFG-E8's role in synapse elimination may extend beyond simple opsonization.
- MFG-E8 might influence synapse elimination through cytoskeletal reorganization in neurons and glial cells.
- The precise conditions and regulatory mechanisms of MFG-E8 in the nervous system require further investigation.
Conclusions:
- MFG-E8 has diverse roles in the nervous system, potentially impacting synapse elimination through multiple pathways.
- Further research is needed to elucidate the context-dependent functions of MFG-E8 in synapse elimination.
- Understanding MFG-E8's role is critical for addressing neuropathologies associated with synapse dysregulation.
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