Lymphocyte polarity, the immunological synapse and the scope of biological analogy

Abstract

We have developed a photoactivation and imaging strategy that enables highresolution analysis of cytoskeletal dynamics in individual T cells. Using this approach, we have demonstrated that the lipid second messenger diacylglycerol plays a crucial role in promoting MTOC reorientation by recruiting three members of the protein kinase C family to the synapse. Here, I will discuss these results along with studies from other labs, which have explored the role of polarityinducing protein complexes after synapse formation. I will also propose a two-step model for MTOC reorientation in lymphocytes that reflects what we now know about the subject. Finally, I will consider the extent to which lymphocyte polarity resembles analogous cell polarity systems in other cell types.Cell polarity is a precondition of multicellular lifestyle. Polarized cells interact with their surroundings in a fundamentally anisotropic manner, which is crucial for establishing systems, such as neuronal circuits, in which there is directional

Lymphocyte Fate and Metabolism: A Clonal Balancing Act

“…The nature and pervasiveness of signaling to unequal cellular outcomes will require further exploration (see Outstanding Questions). Although the PAR polarity network that is commonly associated with apico-basal polarity and asymmetric division was presumed to be the chief architect of lymphocyte asymmetric division, mounting evidence suggests that phospholipid polarity signaling may, instead or in addition, be an integral piece of the puzzle [21, 30, 31, 34, 36-39, 75]. To what extent the PI3K-dependent cell polarity network may intersect with the PAR polarity network still needs to be determined (see Outstanding Questions).…”

“…Nonetheless, motile lymphocytes rely on provisional or facultative polarity to patrol lymphoid tissues in search of trophic ligands for survival and foreign antigens that recruit them for duty [29-32]. Activated lymphocytes also require facultative polarity to form immune synapses critical in signaling, as well as directional endocytosis or exocytosis as part of their essential functions [28, 31, 33]. Extrinsic polarity cues have also been implicated in the organization of asymmetric cell division of lymphocytes [29].…”

“…Extrinsic signaling to a focal area of an interphase lymphocyte results in actin and tubulin cytoskeletal rearrangements and polarized clustering of receptors [8, 27, 28, 31, 35]. Activating receptors co-localize with the centrosome at the site of extrinsic signaling, while inhibitory molecules arrange diametrically opposite at the distal side from the contact.…”

“…Epidermal progenitors undergo apical PI3K-induced polarity and asymmetric division [75]. All of these scenarios are reminiscent of lymphocyte activation with its diametrically opposite arrangement of proximal PI3K activity and distal inhibitory phosphatases [26, 27, 31, 35] (Figure 3). …”

BioArchitecture

“…In the formation of the immunological synapse the reorientation of the microtubule organizing center is mediated by recruitment of multiple members of the protein kinase C family by diacylglycerol 33 . In Chlamydomonas positioning of a photosensory organelle depends on a specific four-membered microtubule rootlet 34 .…”