Organelle Transport: A Park-and-Ride System for Melanosomes

Those of us experiencing graying hair may be more sensitive to the term melanosome than other readers. You will find no remedy within this article, but rather a jealous look at the organisms which are able to manipulate their skin color, for example to match the appearance of their environment. In fish and amphibians, this change is brought about by movements of pigment-containing vesicles, melanosomes, within a special type of epithelial cell, the melanophore. Hormonal stimuli are transmitted to molecular motors which transport the melanosomes along cytoskeletal tracks assembled from actin or tubulin. Because filamentous actin and microtubules have a built-in polarity and certain distributions within the cell, the melanosome movements result in either their homogeneous dispersion within the cytoplasm or the formation of a clump of vesicles in the center of the cell (Figure 1A). As a consequence the cell appears less or more transparent, respectively. A beautiful paper published very recently in Current Biology [1] addresses the question of how this distribution is achieved. The foundation for the present work was laid down within the last decade, when it was first established that Xenopus melanosomes had two microtubule-dependent motors on their surface which work in opposite directions: kinesin II, which transports its cargo towards the plus ends of microtubules in the cell periphery; and cytoplasmic dynein, which mediates aggregation of melanosomes in the center of the cell, where the minus ends of microtubules coalesce into a single spot [2]. Then, about five years ago, two papers published back to back in Current Biology [3,4] established that melanosomes from fish are also able to travel on actin filaments [3], and melanosomes from Xenopus have a bound myosin V motor [4]. Together these findings suggested how melanosomes might move on actin filaments and showed that this type of motility is required for the even distribution of melanosomes within the cell. From these main observations, it became clear that, during aggregation, a cytoplasmic dynein motor carries melanosomes on the radially arranged microtubules towards the cell center (Figure 1B), while during dispersion a kinesin transports the granules to the periphery (Figure 1C), where they engage via a myosin V molecule with short actin filaments to be distributed further (Figure 1D). This switching of transport systems is a kind of miniature edition of modern urban traffic, where millions of workers leave the city centers in the evening on trains and board their cars at park-and-ride stations to complete their daily journey within the green peripheral belt. Besides summarizing the above results into a convincing model, a dispatch published at the time in Current Biology [5] posed the fundamental question of how this concerted activity is brought about. Two possibilities were considered. The first invoked the distribution of actin filaments and microtubules inside cells, which might plausibly govern the switching between transport systems. Because of the radial arrangement of microtubules, their local density is much higher in the center of the cell than at the periphery; and conversely, actin filaments are much more frequent close to the cell perimeter (Figure 1A). Given that different motors may be simultaneously active on a single organelle [6], the probability of encountering a certain type of track may determine the route traveled. But it was known that the stimuli applied to disperse melanosomes lead to marked changes of intracellular second messengers [7]. So it also appeared possible that a signaling cascade might regulate the switching from microtubule tracks to actin filaments. These two alternatives were rigorously tested by Rodionov et al. [1] using the system of cultured fish melanophores and quantitative analysis of individual melanosome motility. To address the first possibility, Rodionov et al. [1] calculated the density of microtubules throughout the cell, taking into account the geometry of the cell and the microtubule length. Then they compared the distances traveled by individual melanosomes in different areas of the cell. Rodionov et al. [1] reasoned that melanosomes should run rather unperturbed close to the center of the cell, whereas they should experience more distraction in the periphery, where microtubules are rare and actin filament density increases. As this was not the case, and such a dependency was not apparent even in the complete absence of actin filaments (elicited by an actin depolymerizing drug), Rodionov et al. [1] concluded that the distribution of melanosomes is not governed by the availability of cytoskeletal tracks. A lot of evidence suggested that the main second messenger produced in response to the dispersion signal, melanocyte-stimulating hormone (MSH), was cAMP. Rodionov et al. [1] therefore chose to carefully compare the production of cAMP to melanosome motility. They observed that, when exposed to a stimulus, the cellular cAMP levels increased steeply, but declined in a biphasic fashion within less than 10 minutes (Figure 1E). Interestingly, these kinetics were precisely paralleled by the distance melanosomes traveled on microtubules towards the periphery of the cell. At the time Dispatch Current Biology, Vol. 13, R917–R919, December 2, 2003, ©2003 Elsevier Science Ltd. All rights reserved. DOI 10.1016/j.cub.2003.11.014