Author: Francesca Del Gaudio
Date: 02/03/2011



Synaptopodin is an actin-associated protein present in podocytes and dendritic spines. It is a linear, proline-rich protein, intimately associated with actin microfilament, and it is expressed in foot process of podocytes in the kidney and in the dendritic spines of the telencephalic synapses. It may play a role in actin-based cell shape and motility. This protein is encoded in humans by the SYNPO gene. The name synaptopodin derives from the protein’s associations with postsynaptic densities and dendritic spines and with renal podocytes.

Myopodin (SYNPO2) is an analog of SYNPO that induces suppression of tumor growth and matastasis


Your Favorite Gene SigmaSYNPOSYNPO2


SYNPO gene is located on the chromosome 5 in human (location 5q33.1). Synaptopodin, also known as KIAA1029, exsists in 3 isoforms:

  • isoform A, 903 aa , also named Sympo-long.

  • isoform B, 685 aa ,differs in the 3’ coding region and 3’ UTR, compared to variant A. Also referred to as Synpo-short, has a distinct C-terminus and is shorter than isoform A.

  • isoform C, 929 aa. This variant has multiple differences compared to variant A. These differences result in a distinct 5’ UTR and cause translation initiation at an alternate start codon as in variant B. The encoded protein is longer than isoform A and contains unique C-termini.

Isoforms Alignement

In rat it was discovered an other isoform named Sympo-T (181 aa).
The SYNPO gene is conserved in chimpanzee, cow, mouse, and rat.

Mature isoform A is O-glycosylated. The sequence of isoform B differs from isoform A because it lacks 1-244 aminoacids.
Isoform B is phosphorylated on Ser-826, Thr-836, Ser-840 and Ser-871. in isoform C phosphorilation sites are absent.

Interesting studies on rats demonstrates that sympo-short contain 2 separate α-actinin binding sites were spanning aa 300–550 and 550–691.

Sympo-long also shares this α- actining binding sites . In addition it harbors 2 additional α -actinin binding sites not found in sympo-short spanning aa 103–159 and 182–227.

Synpo-long form interact with α-4-actinin, while Synpo-short with α-2-actinin.

Synpo-T is a truncated isoform of Synpo-long wich is discovered in synpo / mice.

Synpo-T protein isn’t expressed in brain of wild-type or synpo–/– mice, but it is upregulated in synpo–/– podocytes. Sympo-T had the same capability to bundle and elongate α-actinin-4–induced actin filaments as Synpo-long. Synpo-T serves as functional backup in podocytes of synpo–/– null mice.


When relevant for the function

  • Primary structure
  • Secondary structure
  • Tertiary structure
  • Quaternary structure

Protein Aminoacids Percentage
The Protein Aminoacids Percentage gives useful information on the local environment and the metabolic status of the cell (starvation, lack of essential AA, hypoxia)

Protein Aminoacids Percentage (Width 700 px)

Human synaptopodin is a heat-stable and basic protein with a calculated molecular mass of 73.7 kDa and an isoelectric point of 9.38.
Due to its high content of proline (approx. 20%) evenly distributed along the protein, no formation of any globular domain is possible.

Moreover synaptopodin contains two PPXY motifs (corresponding to aa 318 321 and 337 340 of the human protein) which are involved in protein- protein interactions between proline- rich stretches of different proteins, WW domains and SH3 domains.
The linear conformation of synaptopodin may result in a side to side arrangement along the actin microfilaments


mRNA synthesis

Constraint-based Multiple Alignment Tool

protein synthesis vedi

altri modelli di inizio a UTR interni di proteine:


The distribution of synaptopodin at postsynaptic densities and in dendritc spines is exactly the same for actin in these areas. One of the most exciting features of synaptopodin is that, within the central nervous system, its expression is restricted to exclusively telencephalic post-synaptic densities and associated dendritic spines of the olfactory bulb, cerebral cortex, striatum, and hippocampus. In situ hybridization studies, synaptopodin mRNA is not found in dendrites but in the perikarya only, which may suggest that synaptopodin synthesis is not controlled locally in the dendritic cytoplasm.

Figure 1

Like the post-synaptic densities, podocyte foot processes contain an electron-dense matrix of largely elusive composition. The foot processes are equipped with a microfilament-based contractile apparatus composed of actin, myosin II, a actinin, talin, and vinculin, which is linked to the glomerular basement membrane at focal contacts by integrins complex.
Synaptopodin is associated with the actin microfilaments of podocyte foot processes.

The late appearance of synaptopodin during postnatal brain development follows the maturation of synaptic formations on dendritic spines; equally synaptopodin isn’t expressed by podocyte precursor cells during nephrogenesis but it appears when podocytes started to differentiate and develop their typical process architecture.

Figure 2

The eukaryotic actin cytoskeleton is organized into 2 major forms. The submembranous region is composed of a network of short, branched filaments; deeper in the cortex, in stress fibers,
microvilli, and muscle sarcomeres, actin filaments are much longer and virtually not branched. Synaptopodin specifically interacts with α-actinin and this interaction is functionally significant because synaptopodin bundles and elongates α-actinin–induced actin filaments in an isoform specific manner.
Synpo-short converts α-actinin- 2–induced short, branched actin filaments (AF) into long, unbranched actin filaments that are found in the spine apparatus. Similarly, Synpo-long converts short, cortical α-actinin–induced actin filaments of immature podocytes into long, unbranched contractile filaments found in FPs of differentiated podocytes.

Podocytes foot processes had conctractile protein system (i.e. synaptopodin, actin, myosin) that connect them to slit diaphragm proteins and to glomerular basal membrane (GBM) proteins; these links are crucial for maintenance of foot processes architecture, then for filtration barrier. Lacking of the coordination of this network might cause riorganization of actin cytoskeleton with podocytes foot processes fusion, one of typical features of nephrosic syndrome.
In the absence of synaptopodin, α-actinin induces short, branched actin filaments. Hence, this important protein alter the affinity or avidity of α-actinin for actin, thereby inducing the formation of long, unbranched, parallel bundles.

The expression of synaptopodin coincides with the formation of podocyte foot processes and the development of their parallel contractile actin bundles typical of differentiated adult podocytes, suggesting that synaptopodin induces the typically actin structure of differentiated podocytes. Similarly, in the brain, synaptopodin may induce the long, unbranched actin filaments that are found in the dense plates between the stacks of the dendritic spine apparatus.
The conctractile apparatus of podocytes can respond to vasoactive substances with alteration of this actin cytoskeleton and may provide the basis of foot processes motility. In fact podocytes foot processes are able to retract and to spread out again.
Dendritic fillopodia and their protrusive motility may play important roles in initiation and elimination of synaptic contacts, both during development and synaptic remodelling processes.

  • Enzymes
BRENDA - The Comprehensive Enzyme Information System"URL":
KEGG PathwaysKIIA1029
Human Metabolome Database"URL":
  • Cell signaling and Ligand transport
  • Structural proteins




Involvement of synaptopodin in several diseases:

  • in HIV associated nephropathy there is lost of several markers for all collapsed glomeruli and of synaptopodin from 16% of intact glomeruli, causing renal disfuncion.
  • Srivastava T et al. examined whether an association exists between synaptopodin expression in podocytes and the response to steroids in children with idiopathic nephrosic syndrome and whether synaptopodin expression can be used as a marker of injury.

In experimental animal models, chronic stress leads to neuroanatomic changes in the hippocampus, in particular a decrease in the length and branching of dendrites as well as a decrease in the number of dendritic spines.


Myopodin methylation is associated with clinical outcome in patients with T1G3 bladder cancer. 2010


Podocytes and neurons share many cell biological characteristics. In fact, Some

neuronal degenerative diseases, including Charcot– Marie–Tooth disease, are reported to have lesions also in renal glomeruli. Although these two cell types display totally different functions, to achieve their function it is necessary for both to build up a highly arborized structure that is supported mechanically by the highly organized cytoskeleton. Podocytes and neurons develop long processes, such as podocyte major processes and neuronal axons and dendrites.

Both podocyte foot processes and neuronal dendrites express synaptopodin, that is involved in the actin-reorganization necessary for synaptic plasticity and for the repair of foot processes after transient podocyte damage.

In terms of cytoskeletal elements, branching of processes is achieved by both microtubules and actin filaments which are regulated by Rho family small G-proteins. The Rho family small G-proteins are reported to be responsible for axonal growth, dendritic morphogenesis and podocyte foot process formation.

Process formation of the renal glomerular podocytes: is there common molecular machinery for processes of podocytes and neurons?

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