LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same

Since the discovery of leucine-rich repeat kinase 2 (LRRK2) as a protein that is likely central to the aetiology of Parkinson's disease, a considerable amount of work has gone into uncovering its basic cellular function. This effort has led to the implication of LRRK2 in a bewildering range of cell biological processes and pathways, and probable roles in a number of seemingly unrelated medical conditions. In this review we summarise current knowledge of the basic biochemistry and cellular function of LRRK2. Topics covered include the identification of phosphorylation substrates of LRRK2 kinase activity, in particular Rab proteins, and advances in understanding the activation of LRRK2 kinase activity via dimerisation and association with membranes, especially via interaction with Rab29. We also discuss biochemical studies that shed light on the complex LRRK2 GTPase activity, evidence of roles for LRRK2 in a range of cell signalling pathways that are likely cell type specific, and studies linking LRRK2 to the cell biology of organelles. The latter includes the involvement of LRRK2 in autophagy, endocytosis, and processes at the trans-Golgi network, the endoplasmic reticulum and also key microtubule-based cellular structures. We further propose a mechanism linking LRRK2 dimerisation, GTPase function and membrane recruitment with LRRK2 kinase activation by Rab29. Together these data paint a picture of a research field that in many ways is moving forward with great momentum, but in other ways has not changed fundamentally. Many key advances have been made, but very often they seem to lead back to the same places

Management development: a literature review and implications for future research - Part II: Profiles and Contexts

In this second and concluding part of an extensive review of the management development literature, attention is directed to studies which have sought to describe and explain how managers are in fact made and to studies which have emphasised the contextual aspects of the process. The review is concluded with an overall assessment of the management development literature – its strengths and weaknesses – and with an analysis of the implications which this assessment carries for the conduct of future research. Crucial gaps are identified, not least of which is a general failure to locate descriptions of particular management development initiatives within the context of other ways in which the management stock is enhanced, replenished and managed. Another major shortcoming which is singled out as requiring urgent attention is the failure to place management development accounts and prescriptions within the wider context of organisational characteristics