Our goal is to determine the molecular mechanisms of the myosin-I family of molecular motors. Myosin-Is comprise the largest unconventional myosin family found in humans (eight genes), and its large size and expression profile distinguish it as one of the most diverse. Myosin-Is physically link cell membranes to the underlying actin cytoskeleton where they play essential roles in powering membrane dynamics, membrane trafficking, and mechanical signal- transduction. Myosin-I's show remarkable diversity in their cellular function, which is mediated by their diverse biophysical properties, which includes dynamic tension sensing, membrane- attachment, and unique regulatory modes. Our goal is to provide the biochemical and biophysical foundation for understanding the molecular physiology of this important class of motors. We will use a combination of innovative biophysical techniques to define (1) the structural origin of myosin-I force sensing, (2) the role f myosin-I adaptor proteins in controlling myosin-I activity, and (3) control of myosin-I function by actin regulatory proteins.

Public Health Relevance

Myosin-Is are molecular motors that are expressed in nearly all eukaryotic cells. They are crucial for several normal and pathological processes, including: cell and tissue development, endocytosis, wound healing, hearing, and cell movement. However, the molecular details of myosin-I function in these crucial processes are unknown. Therefore, we will define the basic biochemical and biophysical properties of these motors to better understand the molecular basis of cell physiology and pathology of health-care problems such as metabolic defects, digestion, wound healing, sensory responses, and immunological defense against pathogens.

Agency
National Institute of Health (NIH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM057247-19
Application #
9197660
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Gindhart, Joseph G
Project Start
Project End
Budget Start
Budget End
Support Year
19
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Physiology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Patino-Lopez, Genaro; Aravind, L; Dong, Xiaoyun et al. (2010) Myosin 1G is an abundant class I myosin in lymphocytes whose localization at the plasma membrane depends on its ancient divergent pleckstrin homology (PH) domain (Myo1PH). J Biol Chem 285:8675-86

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