Disease relevance of Prom1

• These findings suggest that loss of prominin causes retinal degeneration, possibly because of impaired generation of the evaginations and/or impaired conversion of the evaginations to disks [1].
• Murine prominin (prom) shows a strong preference for plasma membrane protrusions in a variety of epithelial cells whereas PROML1 is expressed in retinoblastoma cell lines and adult retina [1].
• The AC133 antigen is also expressed on subsets of CD34+ leukemias, suggesting that it may be an important early marker for HSCs, as well as the first described member of a new class of TM receptors [2].
• The injection of CD24+CD133+ PEC but not of CD24-CD133- renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron [3].
• CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133- population is composed mostly of stromal and inflammatory cells [4].

High impact information on Prom1

• Prominin is a novel plasma membrane protein with an N-terminal extracellular domain, five transmembrane segments flanking two short cytoplasmic loops and two large glycosylated extracellular domains, and a cytoplasmic C-terminal domain [5].
• Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells [5].
• In these epithelia, prominin is specific to the apical surface, where it is selectively associated with microvilli and microvilli-related structures [5].
• Remarkably, upon expression in CHO cells, prominin is preferentially localized to plasma membrane protrusions such as filopodia, lamellipodia, and microspikes [5].
• In the adult mouse, prominin has been detected in the brain ependymal layer, and in kidney tubules [5].

Biological context of Prom1

• DNA sequences from Caenorhabditis elegans predict the existence of a protein with the same features, suggesting that prominin is conserved between vertebrates and invertebrates [5].
• A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration [1].
• Here, we report the molecular and cell-biological characterization of four novel prominin-1 splice variants isolated from a mouse testis cDNA library and referred to as prominin-1.s3 to prominin-1.s6 [6].
• Our data suggest that prominin-1 is involved in the formation and/or stabilization of epididymal stereocilia and the tail of spermatozoa, and hence might play a dual role in the biogenesis of spermatozoa [6].
• Surprisingly, due to a single nucleotide deletion that shifts the reading frame and introduces a premature stop codon, the protein predicted from this cDNA would correspond to a C-terminally truncated form of prominin with only four transmembrane segments [7].

Anatomical context of Prom1

• Release of extracellular membrane particles carrying the stem cell marker prominin-1 (CD133) from neural progenitors and other epithelial cells [8].
• Here, we report that in the developing embryonic mouse brain, the fluid in the lumen of the neural tube contains membrane particles carrying the stem cell marker prominin-1 (CD133), a pentaspan membrane protein found on membrane protrusions of the apical surface of neuroepithelial cells [8].
• Immunohistological and electron microscopic analyses show that prominin-1 is: (1) confined to the apical surface of the epithelium all along the epididymal duct, with the exception of the initial segment; (2) concentrated in stereocilia of the epididymal duct epithelium; and (3) found on the tail of developing spermatozoa in seminiferous tubules [6].
• Identification of novel Prominin-1/CD133 splice variants with alternative C-termini and their expression in epididymis and testis [6].
• In early embryos, prominin-1 was expressed in trophoblast but not in cells of the inner cell mass; however, prominin-1 transcripts were detected in undifferentiated ES cells [9].

Associations of Prom1 with chemical compounds

• Prominin-1/CD133 is a five-membrane-span glycoprotein that is thought to act as an organizer of plasma-membrane protrusions [6].
• Lysophosphatidic acid induces clonal generation of mouse neurospheres via proliferation of Sca-1- and AC133-positive neural progenitors [10].

Other interactions of Prom1

• Upon induction of neuronal differentiation, some prominin-1-positive cells, which coexpressed nestin and showed the typical morphology of neural progenitor cells, persisted until terminal stages of differentiation [9].
• Two size classes of prominin-1-containing membrane particles were observed in the ventricular fluid: approximately 600-nm particles, referred to as P2 particles, and 50-80-nm vesicles, referred to as P4 particles [8].
• Thus, MHC II and also the invariant chain belong to a set of proteins comprising the T cell receptor, prominin, and the prion protein, which reside in membrane environments distinct from conventional lipid rafts [11].

Analytical, diagnostic and therapeutic context of Prom1

• Electron microscopy revealed that, within the apical plasma membrane of Caco-2 cells, the AC133 antigen was confined to microvilli and absent from the planar, intermicrovillar regions [12].
• Confocal immunofluorescence and domain-selective cell surface biotinylation experiments on transfected MDCK cells grown on permeable supports demonstrated the virtually exclusive apical localization of prominin at steady state [13].
• Immunoelectron microscopy revealed that prominin was confined to microvilli rather than the planar region of the apical plasma membrane [13].
• The real time PCR analyses indicated that prominin was broadly expressed in different tissues with particularly high levels observed in the kidney and gill of the goldfish [14].
• In addition, data from flow-cytometry indicated that Prominin/CD133, a cell-surface marker for ventricular zone cells, was expressed specifically in these GFP-positive (GFP(+)) cells [15].

References