Biomedical subjects

Peter Knauth

Publications and source records attributed to Peter Knauth.

5 recordsLinked to original sources

PubMed2006

Sorting nexin 17, a non-self-assembling and a PtdIns(3)P high class affinity protein, interacts with the cerebral cavernous malformation related protein KRIT1.

The mammalian sorting nexin (SNX) proteins are involved in the endocytosis and the sorting machinery of transmembrane proteins. Additionally to the family defining phox homology (PX) domain, SNX17 is the only member with a truncated FERM (4.1, ezrin, radixin, and moesin) domain and a unique C-terminal region (together designated as FC unit). By gel filtration and lipid overlay assays we show that SNX17 is a non-self-assembling and a PtdIns(3)P high class affinity protein. A SNX17 affinity to any other phosphoinositides was not detected. By yeast two-hybrid- and GST-trapping assays we identified KRIT1 (krev1 interaction trapped 1) as a new specific interaction partner of the FC unit of SNX17. KRIT1 binds SNX17 by its N-terminal region like the known interaction partner ICAP1alpha (integrin cytoplasmic domain-associated protein-1). The interaction was also detected in HEK 293 cells transiently expressing GFP-tagged KRIT1 and Xpress-tagged SNX17. KRIT1 mutations cause cerebral cavernous malformation (CCM1). Our finding suggests a SNX17 involvement in the indicated KRIT1 function in cell adhesion processes by integrin signaling.

Carrier Proteins↗

PubMed2006

Compensation for unfavorable characteristics of irregular individual shift rotas.

Some employees of TV companies, such as those who produce remote TV programs, have to cope with very irregular rotas and many short-term schedule deviations. Many of these employees complain about the negative effects of such on their wellbeing and private life. Therefore, a working group of employers, council representatives, and researchers developed a so-called bonus system. Based on the criteria of the BESIAK system, the following list of criteria for the ergonomic assessment of irregular shift systems was developed: proportion of night hours worked between 22 : 00 and 01 : 00 h and between 06 : 00 and 07 : 00 h, proportion of night hours worked between 01 : 00 and 06 : 00 h, number of successive night shifts, number of successive working days, number of shifts longer than 9 h, proportion of phase advances, off hours on weekends, work hours between 17 : 00 and 23 : 00 h from Monday to Friday, number of working days with leisure time at remote places, and sudden deviations from the planned shift rota. Each individual rota was evaluated in retrospect. If pre-defined thresholds of criteria were surpassed, bonus points were added to the worker's account. In general, more bonus points add up to more free time. Only in particular cases was monetary compensation possible for some criteria. The bonus point system, which was implemented in the year 2002 for about 850 employees of the TV company, has the advantages of more transparency concerning the unfavorable characteristics of working-time arrangements, incentive for superiors to design "good" rosters that avoid the bonus point thresholds (to reduce costs), positive short-term effects on the employee social life, and expected positive long-term effects on the employee health. In general, the most promising approach to cope with the problems of shift workers in irregular and flexible shift systems seems to be to increase their influence on the arrangement of working times. If this is not possible, bonus point systems may help to achieve greater transparency and fairness in the distribution of unfavorable working-time arrangements within a team, and even reduce the unnecessary unfavorable aspects of shift systems.

Employment↗

PubMed2005

Functions of sorting nexin 17 domains and recognition motif for P-selectin trafficking.

SNX17 is a member of the sorting nexin family (SNX), a group of hydrophilic proteins whose common characteristic property is a phox homology (PX) domain. The PX domain directs SNXs to phosphatidylinositides containing membranes of the endosomal compartment, where the SNXs are involved in the sorting of transmembrane proteins. SNX17 is known to interact with P-selectin and the LDL receptor family. Here, we report that the PX domain of SNX17 specifically binds to phosphatidylinositol 3-phosphate-containing membranes. The functional part of SNX17 that binds P-selectin or Patched (PTCH) consists of a truncated FERM domain and a unique C terminus together (FC-unit). In a yeast two-hybrid analysis a putative recognition motif for the FC-unit was revealed within P-selectin as FxNaa(F/Y). When HepG2 cells overexpress P-selectin together with SNX17, SNX17 changes its distribution from early endosomes to lysobisphosphatidic acid-containing late endosomes. Furthermore, overexpressed SNX17 restrains P-selectin in the outer membrane of the late endosomal compartment, thus preventing the normal lysosomal accumulation of P-selectin. These results suggest that the PX domain is necessary for the intracellular localisation, while the FC-unit is required for cargo recognition. We hypothesise that the expression level of SNX17 may regulate the lysosomal degradation, at least for P-selectin, by suppressing its entry into the inner vesicles of the multi-vesicular bodies (MVBs).

Amino Acid Motifs↗

PubMed2004

Sorting nexin 17 accelerates internalization yet retards degradation of P-selectin.

The transient appearance of P-selectin on the surface of endothelial cells helps recruit leukocytes into sites of inflammation. The tight control of cell surface P-selectin on these cells depends on regulated exocytosis of Weibel-Palade bodies where the protein is stored and on its rapid endocytosis. After endocytosis, P-selectin is either sorted via endosomes and the Golgi apparatus for storage in Weibel-Palade bodies or targeted to lysosomes for degradation. A potential player in this complex endocytic itinerary is SNX17, a member of the sorting nexin family, which has been shown in a yeast two-hybrid assay to bind P-selectin. Here, we show that overexpression of SNX17 in mammalian cells can influence two key steps in the endocytic trafficking of P-selectin. First, it promotes the endocytosis of P-selectin from the plasma membrane. Second, it inhibits the movement of P-selectin into lysosomes, thereby reducing its degradation.

Androstadienes↗

PubMed2003

Preventive and compensatory measures for shift workers.

Shift systems are known to be associated with a variety of psychosocial and physiological problems that can affect the health of workers. This review focuses on measures that can be taken to optimize the well-being of shift workers and to identify ill-health at an early stage. The discussion includes specific aspects of the design of shift systems, taking account of variation in the views and circumstances of employees, and strategies to combat sleepiness at work and elsewhere. Although an ideal shift system does not exist, a wholistic approach comprising education of managers, employees and their families can ameliorate some of the health consequences.

Adaptation, Psychological↗