Fish Synucleins: An Update

Abstract

Synucleins (syns) are a family of proteins involved in several human neurodegenerative diseases and tumors. Since the first syn discovery in the brain of the electric ray Torpedo californica, members of the same family have been identified in all vertebrates and comparative studies have indicated that syn proteins are evolutionary conserved. No counterparts of syns were found in invertebrates suggesting that they are vertebrate-specific proteins. Molecular studies showed that the number of syn members varies among vertebrates. Three genes encode for α-, β- and γ-syn in mammals and birds. However, a variable number of syn genes and encoded proteins is expressed or predicted in fish depending on the species. Among biologically verified sequences, four syn genes were identified in fugu, encoding for α, β and two γ (γ1 and γ2) isoforms, whereas only three genes are expressed in zebrafish, which lacks α-syn gene. The list of "non verified" sequences is much longer and is often found in sequence databases. In this review we provide an overview of published papers and known syn sequences in agnathans and fish that are likely to impact future studies in this field. Indeed, fish models may play a key role in elucidating some of the molecular mechanisms involved in physiological and pathological functions of syn proteins.

Keywords: brain; carp; fish; synuclein; zebrafish.

Figure 1

Cladogram of a ClustalX2 alignment of the ammino acid sequence of fish syns available in the NCBI database and reported in Table 1. The syn isoforms (a = α-syn; b = β-syn; g = γ-syn; s = synuclein, sl = synuclein like) with their accession numbers are shown on the right of the tree. The distance matrix employed maximum likelihood with bootstrapping (500 repetitions). Sequences highlighted in gray, orange, light blue, green and yellow refers to α-syns, β-syns, γ-syns, syn and syn-like, respectively. Arrows indicate human and rat sequences. Main sequence clusters (C) are indicated on the right of the figure.

Figure 2

Synuclein expression in lamprey, zebrafish and carp. (A) Schematic representation of syn gene expression in a parasagittal section of the adult lamprey brain drawn on the base of data published by [66]; (B) Temporal expression pattern of syn genes in zebrafish embryo as described by [70]. The expression of sncb was initially detected in the trigeminal placode (a), then it expanded to ventral diencephalon, olfactory placode, ventral tegmentum, spinal cord neurons (b) and finally it was restricted to the brain and retina (c). The expression of sncga was initially detected in spinal cord neurons and pineal gland (d), afterwards it was detected in hindbrain neurons (e), then it was much prominent in brain and cranial ganglia (f) and finally sncga expression was restricted to the brain and retina (g). The expression of sncgb showed a different spatio-temporal distribution limited only to notochord (h); (C) Spatial expression pattern of syn genes in zebrafish embryo at 24 hpf (h post fertilization) as described by [71]. The sncgb expression is restricted to the notochord, whereas sncb and sncga are expressed in the brain and spinal cord. Red, blue and green dots indicate sncb, sncga and sncgb expression, respectively; (D): Syn genes expression pattern in the main organs of adult zebrafish on the base of results of [72]. Red, blue and green dots indicate sncb, sncga and sncgb expression, respectively; (E): Schematic representation of sncb and sncga expression pattern in a parasagittal section of the adult zebrafish brain drawn on the base of data published by [71]. Red, blue and green dots indicate sncb, sncga and sncgb expression, respectively. The different expression pattern of the two syn genes is well evident: sncb showed a most rostral expression whereas sncga showed a more intensive expression in posterior brain regions; (F): Schematic representation of the expression of α-syn-like proteins in a parasagittal section of the adult carp brain drawn on the base of data published in [73]. Large black dots indicate 3D5 immunoreactive perikarya and small black dots indicate 3D5 immunoreactive varicose fibers.