Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia
*Corresponding author:
Suresh Mathivanan
Department of Biochemistry
La Trobe Institute for Molecular Science
La Trobe University, Melbourne,
Victoria 3086, Australia Tel: +61 03 9479 2506 Fax: +61 03 9479 1226 E-mail:
S.Mathivanan@latrobe.edu.au
Received June 29, 2012; Accepted June 30, 2012; Published July 11, 2012
Citation: Mathivanan S (2012) Exosomes and Shedding Microvesicles are
Mediators of Intercellular Communication: How do they Communicate with the
Target Cells? J Biotechnol Biomater 2:e110. doi:10.4172/2155-952X.1000e110
Intercellular interactions are pivotal for basic cellular activities
and errors in either receiving or transmitting these signals are
shown to cause pathological conditions. Whilst, such intercellular
communications were once thought to be regulated by membrane
surface molecules and/or soluble secreted proteins by stimulating
the target cells through receptor mediated activation, increasing
evidences suggest that extracellular microvesicles (EMVs) can also
trigger such signaling events in the target cells. Exosomes and shedding
microvesicles (SMVs) are classes of EMVs that are membrane enclosed
organelles released by cells under physiological and pathological
conditions [1-6]. Among the EMVs, exosomes are small (40-100 nm
diameter) membraneous vesicles of endocytic origin while SMVs (also
referred to as ectosomes) are large membranous vesicles (50-1000 nm
diameter) that are shed directly from the plasma membrane (PM)
[7]. Recent studies have shown that these EMVs mediate intercellular
communication [8-10] and are shown to harbour mRNA, microRNA,
proteins and lipids [8,11-14] based on the host cell [13].
While many of such recent observations have proven the role
of EMVs in cell-cell communication, the exact mechanism in which
these EMVs communicate with the target cells still remains elusive.
Excluding the study by Rana et al. that showed the role of tetraspanins
in target selection [15], the factors that influence target cell selection
are poorly understood. Possible mechanisms of EMVs communication
with target cells are shown in Figure 1 (exosomes as an example).
EMVs harbor membrane proteins that can interact with the target
cells in a juxtacrine manner, thereby activating the target cell (Figure
1B). Alternatively, exosomes can fuse with the target cell resulting in
the non-selective transfer of exosomal proteins and RNA (Figure 1C)
to the target cell. In addition to proteins and lipids, exosomes also
contain mRNA and microRNAs that can be transferred to the target
cell, conferring new functional properties to the recipient cell after
the acquisition of the exosomal genetic material. Such fusion might
change the membrane features of the target cell (e.g., arachidonic acid
transfer from platelets-derived shedding microvesicles to leukocytes
and endothelial cells [16]) including varied lipid concentrations and
the transfer of exosomal membrane proteins on the target cell surface
(e.g., CD41 antigen from platelets-derived shedding microvesicles to
tumor and endothelia cell surface [17,18]). Proteins that are present
in the soluble secretome are not only a result of protein secretion, cell
death and cell surface membrane ectodomain shedding but also due
to ectodomain shedding of exosomal membrane proteins [19,20].
Exosomal membrane proteins can be cleaved by proteases and the
resulting fragment may act as ligands for cell surface receptor in the
target cell (Figure 1D). In addition to juxtacrine, ectodomain cleavagebased
signaling and membrane fusion, exosomes can be engulfed by
antigen presenting cells and phagocytosized [21] (Figure 1E). The
antigen presenting cells can later process the molecular information
and trigger the cellular signaling cascades [21].
Figure 1
Whilst these are the possible mechanisms of intercellular
communication by EMVs, the precise mechanism need to be clearly
understood to manipulate these bioactive vesicles as efficient drug
delivery vehicles.
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