Goutham Kodakandla - Academia.edu (original) (raw)

Papers by Goutham Kodakandla

Research paper thumbnail of Dynamic S-acylation of STIM1 is required for store-operated Ca2+ entry

Many cell surface stimuli cause calcium release from endoplasmic reticulum (ER) stores to regulat... more Many cell surface stimuli cause calcium release from endoplasmic reticulum (ER) stores to regulate cellular physiology. Upon ER calcium store depletion, the ER-resident protein STIM1 physically interacts with plasma membrane protein Orai1 to induce calcium release-activated calcium (CRAC) currents that conduct calcium influx from the extracellular milieu. Although the physiological relevance of this process is well established, the mechanism supporting the assembly of these proteins is incompletely understood. Earlier we demonstrated a previously unknown post-translational modification of Orai1 with long chain fatty acids, known as S-acylation. We found that S-acylation of Orai1 is dynamically regulated in a stimulus-dependent manner and essential for its function as a calcium channel. Here we show that STIM1 is also rapidly and transiently S-acylated at cysteine 437 upon ER calcium store depletion. S-acylation of STIM1 is required for the assembly of STIM1 into puncta with Orai1 an...

Research paper thumbnail of S-Acylation of STIM1 regulates store-operated calcium entry

Biophysical Journal, 2022

Research paper thumbnail of S-Acylation regulates store-operated calcium entry

Biophysical Journal, 2022

Research paper thumbnail of The Role of S-Acylation in the Regulation of Store-Operated Calcium Entry

Biophysical Journal, 2021

Research paper thumbnail of S-acylation of Orai1 regulates store-operated Ca2+ entry

Journal of Cell Science, 2021

Store-operated Ca2+ entry is a central component of intracellular Ca2+ signaling pathways. The Ca... more Store-operated Ca2+ entry is a central component of intracellular Ca2+ signaling pathways. The Ca2+ release-activated channel (CRAC) mediates store-operated Ca2+ entry in many different cell types. The CRAC channel is composed of the plasma membrane (PM)-localized Orai1 channel and endoplasmic reticulum (ER)-localized STIM1 Ca2+ sensor. Upon ER Ca2+ store depletion, Orai1 and STIM1 form complexes at ER–PM junctions, leading to the formation of activated CRAC channels. Although the importance of CRAC channels is well described, the underlying mechanisms that regulate the recruitment of Orai1 to ER–PM junctions are not fully understood. Here, we describe the rapid and transient S-acylation of Orai1. Using biochemical approaches, we show that Orai1 is rapidly S-acylated at cysteine 143 upon ER Ca2+ store depletion. Importantly, S-acylation of cysteine 143 is required for Orai1-mediated Ca2+ entry and recruitment to STIM1 puncta. We conclude that store depletion-induced S-acylation of O...

Research paper thumbnail of Physiological and Pathological Cardiac Hypertrophy: Molecular Mechanisms and Signaling Pathways *Corresponding author

Cardiovascular disease is one of the most devastating illness across the world causing more numbe... more Cardiovascular disease is one of the most devastating illness across the world causing more number of casualties and deaths every day. Of the multitude of ways through which the normal physiology of conduction system is affected, increase if heart size, also called as Cardiac Hypertrophy (CH), causes a significant number of deaths in affected patients. Cardiac Hypertrophy is classified into Physiological and Pathological variants based on the stimulus that leads to the increase of the size of heart. Also, the effects following the stimulus are different in each variant in regard to signaling events, signaling molecules affected, changes in the anatomy of the heart, etc. There exists clear structural, functional, molecular and metabolic, differences in progression of each variant of CH.

Research paper thumbnail of Dynamic S-acylation of STIM1 is required for store-operated Ca2+ entry

Many cell surface stimuli cause calcium release from endoplasmic reticulum (ER) stores to regulat... more Many cell surface stimuli cause calcium release from endoplasmic reticulum (ER) stores to regulate cellular physiology. Upon ER calcium store depletion, the ER-resident protein STIM1 physically interacts with plasma membrane protein Orai1 to induce calcium release-activated calcium (CRAC) currents that conduct calcium influx from the extracellular milieu. Although the physiological relevance of this process is well established, the mechanism supporting the assembly of these proteins is incompletely understood. Earlier we demonstrated a previously unknown post-translational modification of Orai1 with long chain fatty acids, known as S-acylation. We found that S-acylation of Orai1 is dynamically regulated in a stimulus-dependent manner and essential for its function as a calcium channel. Here we show that STIM1 is also rapidly and transiently S-acylated at cysteine 437 upon ER calcium store depletion. S-acylation of STIM1 is required for the assembly of STIM1 into puncta with Orai1 an...

Research paper thumbnail of S-Acylation of STIM1 regulates store-operated calcium entry

Biophysical Journal, 2022

Research paper thumbnail of S-Acylation regulates store-operated calcium entry

Biophysical Journal, 2022

Research paper thumbnail of The Role of S-Acylation in the Regulation of Store-Operated Calcium Entry

Biophysical Journal, 2021

Research paper thumbnail of S-acylation of Orai1 regulates store-operated Ca2+ entry

Journal of Cell Science, 2021

Store-operated Ca2+ entry is a central component of intracellular Ca2+ signaling pathways. The Ca... more Store-operated Ca2+ entry is a central component of intracellular Ca2+ signaling pathways. The Ca2+ release-activated channel (CRAC) mediates store-operated Ca2+ entry in many different cell types. The CRAC channel is composed of the plasma membrane (PM)-localized Orai1 channel and endoplasmic reticulum (ER)-localized STIM1 Ca2+ sensor. Upon ER Ca2+ store depletion, Orai1 and STIM1 form complexes at ER–PM junctions, leading to the formation of activated CRAC channels. Although the importance of CRAC channels is well described, the underlying mechanisms that regulate the recruitment of Orai1 to ER–PM junctions are not fully understood. Here, we describe the rapid and transient S-acylation of Orai1. Using biochemical approaches, we show that Orai1 is rapidly S-acylated at cysteine 143 upon ER Ca2+ store depletion. Importantly, S-acylation of cysteine 143 is required for Orai1-mediated Ca2+ entry and recruitment to STIM1 puncta. We conclude that store depletion-induced S-acylation of O...

Research paper thumbnail of Physiological and Pathological Cardiac Hypertrophy: Molecular Mechanisms and Signaling Pathways *Corresponding author

Cardiovascular disease is one of the most devastating illness across the world causing more numbe... more Cardiovascular disease is one of the most devastating illness across the world causing more number of casualties and deaths every day. Of the multitude of ways through which the normal physiology of conduction system is affected, increase if heart size, also called as Cardiac Hypertrophy (CH), causes a significant number of deaths in affected patients. Cardiac Hypertrophy is classified into Physiological and Pathological variants based on the stimulus that leads to the increase of the size of heart. Also, the effects following the stimulus are different in each variant in regard to signaling events, signaling molecules affected, changes in the anatomy of the heart, etc. There exists clear structural, functional, molecular and metabolic, differences in progression of each variant of CH.