Biological function of Lemur tyrosine kinase 2 (LMTK2): implications in neurodegeneration

Abstract

Neurodegenerative disorders are frequent, incurable diseases characterised by abnormal protein accumulation and progressive neuronal loss. Despite their growing prevalence, the underlying pathomechanism remains unclear. Lemur tyrosine kinase 2 (LMTK2) is a member of a transmembrane serine/threonine-protein kinase family. Although it was described more than a decade ago, our knowledge on LMTK2’s biological functions is still insufficient. Recent evidence has suggested that LMTK2 is implicated in neurodegeneration. After reviewing the literature, we identified three LMTK2-mediated mechanisms which may contribute to neurodegenerative processes: disrupted axonal transport, tau hyperphosphorylation and enhanced apoptosis. Moreover, LMTK2 gene expression is decreased in an Alzheimer’s disease mouse model. According to these features, LMTK2 might be a promising therapeutic target in near future. However, further investigations are required to clarify the exact biological functions of this unique protein.

Lemur Tyrosine Kinase 2 (LMTK2) Level Inversely Correlates with Phospho-Tau in Neuropathological Stages of Alzheimer’s Disease

“…In a recent review on LMTK2 we proposed that decreased protein activity or expression may contribute to tau hyperphosphorylation [11]. While analysis of LMTK2 signaling is beyond the scope of our current work, recent cell biological studies have shed light on the interaction between phospho-tau and LMTK2.…”

“…The enzyme is involved in the orchestration of vital physiological processes such as axonal transport, apoptosis or neurogenesis [11,12,14,17,18]. Alterations of LMTK2 level may contribute to neurodegeneration by disrupted axonal transport, enhanced apoptosis and tau hyperphosphorylation [11]. We previously described decreased LMTK2 level in human postmortem AD brains compared to age-matched controls [13].…”

“…In general, NFT burden inversely correlates with the number of surviving neurons, proposing that neurofibrillary lesions have a key role in degenerative changes and apoptotic cell loss in AD [10]. The latest studies suggest that there is a link between the expression/activity of recently described lemur tyrosine kinase 2 (LMTK2) protein and tau hyperphosphorylation [11][12][13]. Despite its name, LMTK2 is a member of a membrane-anchored serine/threonine-specific protein kinase family [14][15][16].…”

“…Despite its name, LMTK2 is a member of a membrane-anchored serine/threonine-specific protein kinase family [14][15][16]. The enzyme is involved in the orchestration of vital physiological processes such as axonal transport, apoptosis or neurogenesis [11,12,14,17,18]. Alterations of LMTK2 level may contribute to neurodegeneration by disrupted axonal transport, enhanced apoptosis and tau hyperphosphorylation [11].…”

TheMYO6 interactome: selective motor‐cargo complexes for diverse cellular processes

“…Little is known about the function of this protein compared to other kinases although it has been shown to regulate endocytic trafficking, as well as signalling and apoptosis. Changes in LMTK2 expression and function are linked to neurodegeneration, cancer and defects in spermatogenesis . At present it is not known whether MYO6 activity is regulated through phosphorylation by LMTK2 or whether MYO6 mediates the cellular localization and trafficking of this kinase.…”