Overview
- Peptide CDLIQSK(S)LSKNYTTD, corresponding to amino acid residues 252 - 267 of mouse GRN (Accession P28798). Secreted.
Progranulin Blocking Peptide (BLP-NR178)
Western blot analysis of rat brain lysates (lanes 1 and 3) and rat spleen membranes (lanes 2 and 4):1-2. Anti-Progranulin Antibody (#ANR-178), (1:400).
3-4. Anti-Progranulin Antibody, preincubated with Progranulin Blocking Peptide (BLP-NR178).
Western blot analysis of human U-87 MG glioblastoma cell line lysate (lanes 1 and 5), human K562 myelogenous leukemia cell line lysate (lanes 2 and 6), human MCF-7 breast adenocarcinoma cell line lysate (lanes 3 and 7) and mouse BV-2 microglia cell line lysate (lanes 4 and 8):1-4. Anti-Progranulin Antibody (#ANR-178), (1:400).
5-8. Anti-Progranulin Antibody, preincubated with Progranulin Blocking Peptide (BLP-NR178).
Expression of progranulin in rat hypothalamus.Immunohistochemical staining of perfusion-fixed frozen rat brain sections using Anti-Progranulin Antibody (#ANR-178), (1:100), followed by goat anti-rabbit-AlexaFluor-488. A. Progranulin immunoreactivity (green) appears in neurons (arrows pointing to the left) and along the wall of 3rd ventricle (arrows pointing to the right). B. Pre-incubation of the antibody with Progranulin Blocking Peptide (BLP-NR178), suppressed staining. Cell nuclei are stained with DAPI (blue). 3rd V= Third ventricle.
- Bhandari, V., R.G. Palfree, and A. Bateman (1992) Proc Natl Acad Sci U S A, 89(5): p. 1715-9.
- Kao, A.W., et al. (2017) Nat Rev Neurosci, 18(6): p. 325-333.
- Songsrirote, K., et al. (2010) J Proteomics, 73(8): p. 1479-90.
- Zhu, J., et al. (2002) Cell, 111(6): p. 867-78.
- Kessenbrock, K., et al. (2008) J Clin Invest, 118(7): p. 2438-47.
- Butler, G.S., et al. (2008) Mol Cell Biol, 28(15): p. 4896-914.
- Bai, X.H., et al. (2009) Mol Cell Biol, 2009. 29(15): p. 4201-19.
- Okura, H., et al. (2010) J Atheroscler Thromb, 17(6): p. 568-77.
- Daniel, R., et al. (2000) J Histochem Cytochem, 48(7): p. 999-1009.
- Ryan, C.L., et al. (2009) BMC Neurosci, 10: p. 130.
- Van Damme, P., et al. (2008) J Cell Biol, 181(1): p. 37-41.
- Guo, A., et al. (2010) Brain Res, 1366: p. 1-8.
- Rhinn, H. et al. (2022) Trends Pharmacol. Sci. 43, 641.
The Progranulin (PGRN) protein is encoded by the GRN gene composed of 13 exons, although exon 1 is non-coding. PGRN is a secreted glycoprotein with growth factor like properties, consisting in 7.5 tandem repeats of a 12-cysteine module called granulin or epithelin domain separated by linker regions. The 12-cysteine motif forms six disulfide bridges with the peptide backbone adopting a unique three-dimensional structure of a parallel stack of beta hairpin1,2.
PGRN is synthesized as a 68.5 kDa protein that is N-glycosylated to become a mature secreted 88 kDa protein3. Secreted PGRN is cleaved into 6 kDa granulin peptides, each composed of cysteine repeat motifs. Cleavage of PGRN occurs at the intra-linker spacer regions by several proteases including elastase4, proteinase5, matrix metalloproteinase-146 and ADAM metallopeptidase with thrombospondin type 1 motif7. PGRN cleavage is inhibited by secretory leukocyte protease inhibitor (SLPI)4 and high-density lipoprotein (HDL)/Apolipoprotein A-I complex8.
PGRN is expressed in several tissues showing a prominent expression in epithelial, immune and, neuronal cells9. In particular, a strong expression of PGRN mRNA was found in highly proliferative epithelia including those of the intestinal crypt, skin, and reproductive tracts9. In contrast, PGRN shows low expression in less proliferative and highly differentiated cells such as those of alveolar lung and renal tube epithelia9.
PGRN shows high expression in peripheral immune system tissues such as spleen and lymph nodes9 and is also highly expressed in the central nervous system (CNS) with expression in both neurons and neuroinflammatory cells. PGRN has been detected in neurons of the neocortex, hippocampus, arcuate nucleus and ventromedial hypothalamus, Purkinje cells of the cerebellum and in motor neurons9. In the CNS, PGRN can function as neurotrophic growth factor increasing cell viability10 and neurite outgrowth [11]. PGRN knockdown in rat hippocampal neurons results in decreased neuronal arborization and length and synaptic densities12 showing its role in neuronal morphology and establishing interneuron connections.
Several proteins have been identified as receptors for GPRN, including Sortilin, which is considered the major regulator of GPRN in the brain, as well as, EphA2, LRP1, Notch and more13.
Loss of function mutations in the GRN gene, cause a range of neurodegenerative disorders including frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's and Parkinson's disease 13.
Anti-Progranulin Antibody (#ANR-178) is a highly specific antibody directed against an epitope of the mouse protein. The antibody can be used in western blot and immunohistochemistry applications. It has been designed to recognize Progranulin from rat, mouse and human samples.
Powered by Bioz
