ALK (Anaplastic Lymphoma Kinase) expression in DRG neurons and its involvement in neuron-Schwann cells interaction.

ABSTRACT

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) transiently expressed in specific regions of the central and peripheral nervous systems. In this study, we focused on the rat developing dorsal root ganglion (DRG). This ganglion is composed of heterogeneous sensory neurons characterized by the expression of RTK for neurotrophic factors, such as the nerve growth factor receptor TrkA or the glial-derived neurotrophic factor family receptor Ret, which are specifically detected in nociceptive neurons. In DRG, ALK expression reached a maximum around birth. We showed that ALK is specifically present in a subtype of neurons during DRG development, and that the majority of these neurons co-expressed TrkA and Ret. Interestingly, we identified only one form (220 kDa) of ALK in DRG neurons both in vivo and in vitro. On the opposite, in transfected cells as well as in brain extracts, ALK was identified as two forms (220 and 140 kDa). The DRG is composed of neurons and glial cells, principally satellite Schwann cells. Thus, we hypothesized that the presence of satellite Schwann cells was involved in the absence of truncated ALK. Using two different cell types, HEK293 cells stably expressing ALK, and MSC80 cells, a previously described Schwann cell line, we showed that a factor secreted by the Schwann cells is likely involved in the absence of ALK cleavage. All these data hence open new perspectives concerning the role of ALK in the specification of nociceptive DRG neurons and in the neurons-Schwann cells interaction.