Cell-to-cell communication is a crucial
prerequisite for the development and maintenance of multicellular organisms. Since the report by Rustom et al. that cultured
cells are capable of forming “nanotubes” that span up to several cell diameters
in length and that they use these conduits to transport whole organelles
between cells (1), the last decade has seen a burst of interest in the phenomenon
of intercellular organelle exchange and transfer. Traditionally considered
processes of intercellular communication include cell contact dependent and
paracrine receptor-ligand interactions, synaptic vesicle release and uptake,
and ion flow through gap junctions (2). However, organelle transfer is in a
sense a special form of intercellular communication, because it represents the
transfer not only of signals but also of defined intracellular structures.
Image from Science 303: 1007–1010, (2004). Figure 1
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The tunneling
nanotubes (TNTs) had a diameter of 50 to 200 nm and a length of up to several
cell diameters (Fig. 1, A to G). TNTs rarely displayed a branched appearance (Fig. 1C, arrow). Furthermore, they were stretched
between interconnected cells attached at their nearest distance and did not
contact the substrate (Fig. 1D). TNTs contained F-actin but not microtubules (Fig. 1E). When was performed scanning electron
microscopic (SEM) analysis, the stretched shape and structure of TNTs could be
preserved, and their surface showed a seamless transition to the surface of
both connected cells (Fig. 1F). Transmission
electron microscopic (TEM) analysis changed the stretched morphology of TNTs
into a bent configuration presumably because of mechanical stress during sample
preparation. However, serial sectioning showed that, at any given point along
TNTs, their membrane appeared to be continuous with the membranes of connected
cells (Fig. 1G).
More than 40
variations of intercellular organelle transfer have been described, including
endoplasmic reticulum/Golgi bodies, endosomes, lysosomes or the
lysosome-related melanosome, and mitochondria originating in one cell
(organelle donor) and being transported to another (organelle recipient).Intercellular
organelle transfer has been demonstrated to be crucial to several experimental
models of cell survival under external stress. However, evidence for its role
in cellular reprogramming is less robust. The consequences of intercellular
organelle transfer are: enhancing probability of cell survival and cellular reprogramming
(3).The study of intercellular organelle transfer has burgeoned in parallel
with the study of “tunneling nanotubes,” the principal conduit through which
organelles travel from one cell to the other. In multiple studies, organelle
motion in nanotubes has been visualized during the process of intercellular
organelle transfer (1). Real-time studies by fluorescence microscopy indicate
that that the nanotube protrudes from the initiating cell as an extension of
the plasma membrane. Two lines of evidence suggest that nanotubes are both
sufficient and necessary as the structural bridge for intercellular organelle
transfer. They are sufficient because, when cultured under cooled conditions in
which nanotube formation occurs, but other transfer processes such as
endocytosis, exocytosis, and phagocytosis are blocked, intercellular organelle
transfer is sustained between rat pheocromocytoma cells and rat kidney cells
(1). However, the mechanism that preserves nanotube transport under cooled
conditions remains unclear.
The
future therapeutic implications of this research need to consider strategies to
pharmacologically augment intercellular organelle transfer when desirable
(i.e., to replenish dysfunctional mitochondrial and lysosomes in the cell under
stress) or block its occurrence when it is deleterious, such as in the spread
of infection or the maintenance of malignant cells. More recently, Julia Ranzinger, Amin Rustom and Vedat
Schwenger (4) showed the existence
of nanotubular connections between human primary peritoneal mesothelial cells
(HPMCs) and provided insights to their actin/filopodia mediated building
mechanism. They showed also that TNF significantly increased TNTs formation
between HPMCs, pointing to a crucial role of TNTs during inflammatory processes
(4).
References:
1. Rustom A, Saffrich R, Markovic I, Walther P, Gerdes
HH. Nanotubular highways for intercellular organelle transport. Science 303:
1007–1010, (2004).
2. Alberts B, Johnson A, Lewis J, Raff M, Roberts K,
Walter P. Molecular.Biology of the Cell. New York: Garland Science,
2008.
3. Robert S. Rogers, Jahar Bhattacharya. When cells
become organelle donors. Physiology 28:
414–422,2013
4. Julia Ranzinger, Amin Rustom, Vedat Schwenger. Potential role of nanotubes in context of clinical
treatments? Communicative & Integrative Biology 2013 January 1, 6 (1): e22686
Phileno Pinge-Filho - UEL
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