Synaptojanin

Introduction of Synaptojanin

Functioning as a neuronal phosphoinositide phosphatase, synaptojanin mainly hydrolyzes phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) to facilitate membrane trafficking and synaptic vesicle (SV) recycling at presynaptic terminals. Deletion or dysfunction of synaptojanin may lead to severe synaptic defects, such as depletion of SVs, accumulation of endocytic intermediates, and subsequent failure in synaptic transmission.

Structure of Synaptojanins

Synaptojanins belong to the synaptojanin family, which includes two main proteins, synaptojanin 1 (SYNJ1) and synaptojanin 2 (SYNJ2). SYNJ1 is evolutionarily well conserved and enriched at synapses. Synaptojanins consist of three domains:

• A central inositol 5-phosphatase domain (IPPc), which can act on both phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and phosphatidylinositol (4,5)-bisphosphate(PIP2).
• A Sac1-like inositol phosphatase domain at the N-terminus, which hydrolyzes PI(3)P, PI(4)P, and PI(3,5)P2 to PI.
• A C-terminal proline-rich domain (PRD) that interacts with several proteins involved in vesicle endocytosis, such as amphiphysin, endophilin, DAP160/intersectin, syndapin, and Eps15. PRD contains at least five potential Src homology 3 (SH3) domain-binding consensus sequences.

The structure of SYNJ1 with dual phosphatase activity is required for efficient synaptic vesicle endocytosis and reavailability at nerve terminals.

Fig.1 Functional and interaction domains of the two major isoforms of SYNJ1. (Drouet, 2014)

Function of Synaptojanins

Due to different functional domains, synaptojanins play crucial roles in nerve terminals, coupling endocytic vesicle fission, phosphoinositide dephosphorylation, synaptic vesicle recycling, and endocytosis. Moreover, synaptojanins also take part in similar mechanisms in cone photoreceptors, hair cells, podocyte foot processes.

• Function in Neurons

SYNJ1 is highly enriched in presynaptic nerve terminals. Similar to dynamin, SYNJ1 interacts with amphiphysin and undergoes dephosphorylation after nerve terminal depolarization. Numerous studies have revealed that SYNJ1 not only involves endocytic and postendocytic mechanisms presynaptically, but also participates in the signal transmission through postsynaptic reorganization. SYNJ1-deficient mice exhibit neurological defects, such as severe weakness, ataxia, spontaneous epileptic seizures, and poor motor coordination and die shortly after birth.

Fig.2 SYNJ1 participates in synaptic vesicle recycling and PD. (Drouet, 2014)

• Function in Other Cell Types

In podocytes, SYNJ1, interacting with dynamin and endophilin, participates in endocytosis by acting on phosphoinositides and actin filaments. This is required for efficient glomerular filtration and proper renal function. SYNJ1 has been recently reported as a potential regulator of allogeneic T cell responses.

Synaptojanins are associated with synaptic dysfunction in bipolar disorder, Down’s syndrome, Parkinson’s disease, and Alzheimer’s disease. Therefore, the study of synaptojanins is of particular interest to dissect the neuropathological processes involved and to find potential therapeutic targets to counteract these neuropathic diseases. As a leading service provider in neuroscience, Creative Biolabs now provides a variety of antibodies, proteins, agonists/antagonists, toxins against various targets in synaptojanins, and the related endocytosis pathways to meet our clients’ requirements. We also provide one-stop customized development services for our clients. If you are interested in our services and products, please do not hesitate to contact us for more detailed information.

Reference

1. Drouet, V.; Lesage, S. Synaptojanin 1 mutation in Parkinson’s disease brings further insight into the neuropathological mechanisms. BioMed research international. 2014, 2014.