Release of extracellular membrane particles carrying the stem cell marker prominin-1 (CD133) from neural progenitors and other epithelial cells

Abstract

Apical plasma membrane constituents of mammalian neural stem/progenitor cells have recently been implicated in maintaining their stem/progenitor cell state. 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. Two size classes of prominin-1-containing membrane particles were observed in the ventricular fluid: ≈600-nm particles, referred to as P2 particles, and 50-80-nm vesicles, referred to as P4 particles. The P2 and P4 particles appeared in the ventricular fluid at the very onset and during the early phase of neurogenesis, respectively. Concomitant with their appearance, the nature of the prominin-1-containing apical plasma membrane protrusions of neuroepithelial cells changed, in that microvilli were lost and large pleiomorphic protuberances appeared. P4 particles were found in various body fluids of adult humans, including saliva, seminal fluid and urine, and were released by the epithelial model cell line Caco-2 upon differentiation. Importantly, P4 particles were distinct from exosomes. Our results demonstrate the widespread occurrence of a novel class of extracellular membrane particles containing proteins characteristic of stem cells, and raise the possibility that the release of the corresponding membrane subdomains from the apical surface of neural progenitors and other epithelial cells may have a role in tissue development and maintenance. Moreover, the presence of prominin-1-containing membrane particles in human body fluids may provide the basis for a protein-based diagnosis of certain diseases.

A Comparative Proteomic Analysis of Human and Rat Embryonic Cerebrospinal Fluid

“…The relatively high percentage of membrane proteins is consistent with the recent discovery of membrane bound particles in the CSF. 1 Out of 188 proteins found in the human e-CSF, 19% are cytoplasmic proteins, 16% are secreted proteins found in the extracellular space or extracellular matrix (ECM), 14% are nuclear proteins, and 9% are intracellular proteins that could not be specifically localized to one compartment. Out of 137 proteins present in all rat e-CSF samples, 14% are cytoplasmic proteins, 15% are ECM proteins, 3% are nuclear proteins, and 12% are intracellular proteins.…”

The Apical Polarity Determinant Crumbs 2 Is a Novel Regulator of ESC-Derived Neural Progenitors

“…1K). Crb2 localization was also associated with the apical fate determinant and neural stem cell marker prominin1 [35,36] in neural rosette cells (Supporting Information Figure 3C). However, Crb2 expression was excluded from basally located TuJ1-positive neurons (Fig.…”

Apical and lateral cell protrusions interconnect epithelial cells in live Drosophila wing imaginal discs

“…Intercellular communication is important for the growth and patterning of tissues and organs and cell protrusions may mediate this communication by one of several mechanisms. Signaling mediated by cell protrusions can occur by means of transport and local release of signalling molecules, shedding of vesicles (Marzesco et al, 2005), display of receptors (Tomlinson et al, 1987;Hsiung et al, 2005) and membrane-tethered ligands on the protrusion (De Joussineau et al, 2003), or by establishing direct organelle exchange between connected cells (Rustom et al, 2004;reviewed in Demontis, 2004).…”